EOS Med Chem produce AT-7519,902135-91-5 in GMP plant, C-GMP standard, now COA, NMR, HPLC, MS is ok.

Name: AT-7519 HCl
CAS#: 902135-91-5 (HCl salt)
Chemical Formula: C16H17Cl2N5O2
Exact Mass:
Molecular Weight: 418.71
Elemental Analysis: C, 45.90; H, 4.33; Cl, 25.40; N, 16.73; O, 7.6


EOS Med Chem produce AT-7519,902135-91-5 in GMP plant, C-GMP standard, now COA, NMR, HPLC, MS is ok.
AT-7519,902135-91-5 Intermediates, EOS Med Chem have 8; AT-7519,902135-91-5 Impurity we have 10, all from GMP, FDA plant.
Now AT-7519,902135-91-5 DMF document is preparing.
Until 2016, Aug, AT-7519,902135-91-5 more than produced 25kg API, 120kg Intermediates

GMP PRODUCE:

Alectinib;Veliparib;Acalabrutinib;Venetoclax;Sotagliflozin;Ledipasvir;LX1606;Anacetrapib;Abemaciclib 

2016 Mumbai CPHI, Hope to meet!

2016 Barcelona CPHI, Hope to meet!

2016 Korea(한국) CPHI, C40, Welcome!

2016 Shanghai CPHI, W5C47, Welcome!

EOS Med Chem, Medchem is Big

執大象，天下往，往而無害，安平泰

網址: www.eosmedchem.com 

郵箱: gutian@eosmedchem.com; eosmedchem@gmail.com 

辦公室: 0086-531-69905422-806(直通)

攜帶番號 & WhatsApp: +8618653174435

Skype: willgutian

AT-7519 AT-7519 844442-38-2(free base)
AT-7519M AT-7519M 902135-91-5(HCl)
AT-7519 Intermediates 4-[(4-amino-1H-pyrazole-3-carbonyl)amino]piperidine-1-carboxylic acid tert-butyl ester 844443-81-8
AT-7519 Intermediates 4-(2,6-dichloro-benzoylamino)-1H-pyrazole-3-carboxylic acid 825619-04-3


Description: AT-7519 is an orally bioavailable small molecule CDK inhibitor with potential antineoplastic activity. AT7519M selectively binds to and inhibits cyclin dependent kinases (CDKs), which may result in cell cycle arrest, induction of apoptosis, and inhibition of tumor cell proliferation. CDKs are serine/theronine kinases involved in regulation of the cell cycle and may be overexpressed in some types of cancer cells.
Synonym: AT7519; AT-7519; AT 7519.
IUPAC/Chemical Name: N-(4-Piperidinyl)-4-(2,6-dichlorobenzoylamino)-1H-pyrazole-3-carboxamide hydrochloride
SMILES Code: O=C(C1=NNC=C1NC(C2=C(Cl)C=CC=C2Cl)=O)NC3CCNCC3.[H]Cl


Related:
902135-91-5 (AT-7519 HCl salt)
844442-38-2 (AT-7519 free base)
1: Lucas CD, Dorward DA, Tait MA, Fox S, Marwick JA, Allen KC, Robb CT, Hirani N, Haslett C, Duffin R, Rossi AG. Downregulation of Mcl-1 has anti-inflammatory pro-resolution effects and enhances bacterial clearance from the lung. Mucosal Immunol. 2013 Nov 27. doi: 10.1038/mi.2013.102. [Epub ahead of print] PubMed PMID: 24280938.
2: Dolman ME, den Hartog IJ, Molenaar JJ, Schellens JH, Beijnen JH, Sparidans RW. Liquid chromatography-tandem mass spectrometric assay for the cyclin-dependent kinase inhibitor AT7519 in mouse plasma. J Pharm Biomed Anal. 2014 Jan 25;88:216-20. doi: 10.1016/j.jpba.2013.08.051. Epub 2013 Sep 12. PubMed PMID: 24080524.
3: Alessandri AL, Duffin R, Leitch AE, Lucas CD, Sheldrake TA, Dorward DA, Hirani N, Pinho V, de Sousa LP, Teixeira MM, Lyons JF, Haslett C, Rossi AG. Induction of eosinophil apoptosis by the cyclin-dependent kinase inhibitor AT7519 promotes the resolution of eosinophil-dominant allergic inflammation. PLoS One. 2011;6(9):e25683. doi: 10.1371/journal.pone.0025683. Epub 2011 Sep 30. PubMed PMID: 21984938; PubMed Central PMCID: PMC3184151.
4: Mahadevan D, Plummer R, Squires MS, Rensvold D, Kurtin S, Pretzinger C, Dragovich T, Adams J, Lock V, Smith DM, Von Hoff D, Calvert H. A phase I pharmacokinetic and pharmacodynamic study of AT7519, a cyclin-dependent kinase inhibitor in patients with refractory solid tumors. Ann Oncol. 2011 Sep;22(9):2137-43. doi: 10.1093/annonc/mdq734. Epub 2011 Feb 16. PubMed PMID: 21325451.
5: Squires MS, Cooke L, Lock V, Qi W, Lewis EJ, Thompson NT, Lyons JF, Mahadevan D. AT7519, a cyclin-dependent kinase inhibitor, exerts its effects by transcriptional inhibition in leukemia cell lines and patient samples. Mol Cancer Ther. 2010 Apr;9(4):920-8. doi: 10.1158/1535-7163.MCT-09-1071. Epub 2010 Mar 30. PubMed PMID: 20354122.
6: Santo L, Vallet S, Hideshima T, Cirstea D, Ikeda H, Pozzi S, Patel K, Okawa Y, Gorgun G, Perrone G, Calabrese E, Yule M, Squires M, Ladetto M, Boccadoro M, Richardson PG, Munshi NC, Anderson KC, Raje N. AT7519, A novel small molecule multi-cyclin-dependent kinase inhibitor, induces apoptosis in multiple myeloma via GSK-3beta activation and RNA polymerase II inhibition. Oncogene. 2010 Apr 22;29(16):2325-36. doi: 10.1038/onc.2009.510. Epub 2010 Jan 25. PubMed PMID: 20101221; PubMed Central PMCID: PMC3183744.
7: Squires MS, Feltell RE, Wallis NG, Lewis EJ, Smith DM, Cross DM, Lyons JF, Thompson NT. Biological characterization of AT7519, a small-molecule inhibitor of cyclin-dependent kinases, in human tumor cell lines. Mol Cancer Ther. 2009 Feb;8(2):324-32. doi: 10.1158/1535-7163.MCT-08-0890. Epub 2009 Jan 27. PubMed PMID: 19174555.
8: Wyatt PG, Woodhead AJ, Berdini V, Boulstridge JA, Carr MG, Cross DM, Davis DJ, Devine LA, Early TR, Feltell RE, Lewis EJ, McMenamin RL, Navarro EF, O'Brien MA, O'Reilly M, Reule M, Saxty G, Seavers LC, Smith DM, Squires MS, Trewartha G, Walker MT, Woolford AJ. Identification of N-(4-piperidinyl)-4-(2,6-dichlorobenzoylamino)-1H-pyrazole-3-carboxamide (AT7519), a novel cyclin dependent kinase inhibitor using fragment-based X-ray crystallography and structure based drug design. J Med Chem. 2008 Aug 28;51(16):4986-99. doi: 10.1021/jm800382h. Epub 2008 Jul 26. PubMed PMID: 18656911.

EOS Med Chem produce Palbociclib,PD-0332991, 827022-32-2 in GMP plant, C-GMP standard, now COA, NMR, HPLC, MS is ok.

Name: Palbociclib HCl

CAS#: 827022-32-2 (HCl)

Chemical Formula: C24H29N7O2

Exact Mass:

Molecular Weight: 483.99

Elemental Analysis: C, 59.56; H, 6.25; Cl, 7.33; N, 20.26; O, 6.61

GMP PRODUCE:

Alectinib;Veliparib;Acalabrutinib;Venetoclax;Sotagliflozin;Ledipasvir;LX1606;Anacetrapib;Abemaciclib 

2016 Mumbai CPHI, Hope to meet!

2016 Barcelona CPHI, Hope to meet!

2016 Korea(한국) CPHI, C40, Welcome!

2016 Shanghai CPHI, W5C47, Welcome!

EOS Med Chem, Medchem is Big

執大象，天下往，往而無害，安平泰

網址: www.eosmedchem.com 

郵箱: gutian@eosmedchem.com; eosmedchem@gmail.com 

辦公室: 0086-531-69905422-806(直通)

攜帶番號 & WhatsApp: +8618653174435

Skype: willgutian

EOS Med Chem produce Palbociclib,PD-0332991, 827022-32-2 in GMP plant, C-GMP standard, now COA, NMR, HPLC, MS is ok.

Palbociclib,PD-0332991, 827022-32-2 Intermediates, EOS Med Chem have 8; Palbociclib,PD-0332991, 827022-32-2 Impurity we have 10, all from GMP, FDA plant.

Now Palbociclib,PD-0332991, 827022-32-2 DMF document is preparing.

Until 2016, Aug, Palbociclib,PD-0332991, 827022-32-2 more than produced 25kg API, 120kg Intermediates

Palbociclib Ibrance;PD-0332991;Palbociclib;; 571190-30-2(free base)

Palbociclib HCl Ibrance;PD-0332991;Palbociclib;PD-0332991 HCl; 827022-32-2(HCl)

Palbociclib Intermediates 1-(6-nitropyridin-3-yl)piperazine 775288-71-6

Palbociclib Intermediates tert-butyl 4-(6-nitropyridin-3-yl)piperazine-1-carboxylate 571189-16-7

Palbociclib Intermediates 6-bromo-2-chloro-8-cyclopentyl-5-methylpyrido[2,3-d]pyrimidin-7(8H)-one 1016636-76-2

Palbociclib Intermediates 5-bromo-2-chloro-N-cyclopentylpyrimidin-4-amine 733039-20-8

Palbociclib Intermediates 2-chloro-8-cyclopentyl-5-Methylpyrido[2,3-d]pyriMidin-7(8H)-one 1013916-37-4

Palbociclib Intermediates Tert-butyl 4-(6-aminopyridin-3-yl)piperazine-1-carboxylate 571188-59-5

Palbociclib Intermediates Tert-butyl 4-(6-((6-bromo-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3-d]pyrimidin-2-yl)amino)pyridin-3-yl)piperazine-1-carboxylate 571188-82-4

Palbociclib Intermediates Tert-butyl 4-(6-((6-(1-butoxyvinyl)-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3-d]pyrimidin-2-yl)amino)pyridin-3-yl)piperazine-1-carboxylate

Palbociclib Intermediates 6-bromo-8-cyclopentyl-5-methyl-2-(methylsulfinyl)pyrido[2,3-d]pyrimidin-7(8H)-one 571188-81-3

Palbociclib Intermediates Ethyl 4-(cyclopentylamino)-2-(methylthio)pyrimidine-5-carboxylate 211245-62-4

Palbociclib Intermediates (4-(cyclopentylamino)-2-(methylthio)pyrimidin-5-yl)methanol 211245-63-5

Palbociclib Intermediates 4-(cyclopentylamino)-2-(methylthio)pyrimidine-5-carbaldehyde 211245-64-6

Palbociclib Intermediates 1-(4-(cyclopentylamino)-2-(methylthio)pyrimidin-5-yl)ethanol 362656-31-3

Palbociclib Intermediates 8-cyclopentyl-5-methyl-2-(methylthio)pyrido[2,3-d]pyrimidin-7(8H)-one 362656-23-3

Description: Palbociclib, also known as PD0332991, is an orally available pyridopyrimidine-derived cyclin-dependent kinase (CDK) inhibitor with potential antineoplastic activity. PD-0332991 selectively inhibits cyclin-dependent kinases (particularly Cdk4/cyclin D1 kinase), which may inhibit retinoblastoma (Rb) protein phosphorylation; inhibition of Rb phosphorylation prevents Rb-positive tumor cells from entering the S phase of the cell cycle (arrest in the G1 phase), resulting in suppression of DNA replication and decreased tumor cell proliferation. PD 0332991 is a highly specific inhibitor of cyclin-dependent kinase 4 (Cdk4) (IC50 = 0.011 μmol/L) and Cdk6 (IC50 = 0.016 μmol/L), having no activity against a panel of 36 additional protein kinases. Palbociclib was approved on 2/3/2015 for treatment of advanced (metastatic) breast cancer.

Synonym: PD 0332991; PD-0332991; PD0332991; PD0332991; PD332991; PD-332991; PD 332991; Palbociclib, brand name: Ibrance

IUPAC/Chemical Name: 6-acetyl-8-cyclopentyl-5-methyl-2-((5-(piperazin-1-yl)pyridin-2-yl)amino)pyrido[2,3-d]pyrimidin-7(8H)-one hydrochloride

SMILES Code: O=C1C(C(C)=O)=C(C)C2=CN=C(NC3=NC=C(N4CCNCC4)C=C3)N=C2N1C5CCCC5.[H]Cl

CAS# related to Palbociclib

CAS#571190-30-2 (Palbociclib free base);

CAS# 827022-32-2 ( PalbociclibHCl salt);

CAS#827022-33-3 (Palbociclib Isethionate)

1: L'Allemain G. [Doubling time of progression-free survival by palbociclib in metastatic breast cancer]. Bull Cancer. 2015 Apr;102(4):300. doi: 10.1016/j.bulcan.2015.02.011. French. PubMed PMID: 26042255.

2: Palbociclib Extends Survival in Advanced Breast Cancer. Cancer Discov. 2015 Jun 2. [Epub ahead of print] PubMed PMID: 26036642.

3: Turner NC, Ro J, André F, Loi S, Verma S, Iwata H, Harbeck N, Loibl S, Huang Bartlett C, Zhang K, Giorgetti C, Randolph S, Koehler M, Cristofanilli M. Palbociclib in Hormone-Receptor-Positive Advanced Breast Cancer. N Engl J Med. 2015 Jun 1. [Epub ahead of print] PubMed PMID: 26030518.

4: Niesvizky R, Badros AZ, Costa LJ, Ely SA, Singhal SB, Stadtmauer EA, Haideri NA, Yacoub A, Hess G, Lentzsch S, Spicka I, Chanan-Khan AA, Raab MS, Tarantolo S, Vij R, Zonder JA, Huang X, Jayabalan D, Di Liberto M, Huang X, Jiang Y, Kim ST, Randolph S, Chen-Kiang S. Phase 1/2 study of cyclin-dependent kinase (CDK)4/6 inhibitor palbociclib (PD-0332991) with bortezomib and dexamethasone in relapsed/refractory multiple myeloma. Leuk Lymphoma. 2015 May 15:1-9. [Epub ahead of print] PubMed PMID: 25813205.

5: Dhillon S. Palbociclib: first global approval. Drugs. 2015 Apr;75(5):543-51. doi: 10.1007/s40265-015-0379-9. PubMed PMID: 25792301.

6: Finn RS, Crown JP, Lang I, Boer K, Bondarenko IM, Kulyk SO, Ettl J, Patel R, Pinter T, Schmidt M, Shparyk Y, Thummala AR, Voytko NL, Fowst C, Huang X, Kim ST, Randolph S, Slamon DJ. The cyclin-dependent kinase 4/6 inhibitor palbociclib in combination with letrozole versus letrozole alone as first-line treatment of oestrogen receptor-positive, HER2-negative, advanced breast cancer (PALOMA-1/TRIO-18): a randomised phase 2 study. Lancet Oncol. 2015 Jan;16(1):25-35. doi: 10.1016/S1470-2045(14)71159-3. Epub 2014 Dec 16. PubMed PMID: 25524798.

7: Vaughn DJ, Hwang WT, Lal P, Rosen MA, Gallagher M, O'Dwyer PJ. Phase 2 trial of the cyclin-dependent kinase 4/6 inhibitor palbociclib in patients with retinoblastoma protein-expressing germ cell tumors. Cancer. 2015 May 1;121(9):1463-8. doi: 10.1002/cncr.29213. Epub 2014 Dec 18. PubMed PMID: 25522918.

8: DeMichele A, Clark AS, Tan KS, Heitjan DF, Gramlich K, Gallagher M, Lal P, Feldman M, Zhang P, Colameco C, Lewis D, Langer M, Goodman N, Domchek S, Gogineni K, Rosen M, Fox K, O'Dwyer P. CDK 4/6 inhibitor palbociclib (PD0332991) in Rb+ advanced breast cancer: phase II activity, safety, and predictive biomarker assessment. Clin Cancer Res. 2015 Mar 1;21(5):995-1001. doi: 10.1158/1078-0432.CCR-14-2258. Epub 2014 Dec 11. PubMed PMID: 25501126.

9: Altenburg JD, Farag SS. The potential role of PD0332991 (Palbociclib) in the treatment of multiple myeloma. Expert Opin Investig Drugs. 2015 Feb;24(2):261-71. doi: 10.1517/13543784.2015.993753. Epub 2014 Dec 13. PubMed PMID: 25494820.

10: Schultz KA, Petronio J, Bendel A, Patterson R, Vaughn DJ. PD0332991 (Palbociclib) for treatment of pediatric intracranial growing teratoma syndrome. Pediatr Blood Cancer. 2015 Jun;62(6):1072-4. doi: 10.1002/pbc.25338. Epub 2014 Nov 21. PubMed PMID: 25417786.

11: de Melo-Diogo D, Gaspar VM, Costa EC, Moreira AF, Oppolzer D, Gallardo E, Correia IJ. Combinatorial delivery of Crizotinib-Palbociclib-Sildenafil using TPGS-PLA micelles for improved cancer treatment. Eur J Pharm Biopharm. 2014 Nov;88(3):718-29. doi: 10.1016/j.ejpb.2014.09.013. Epub 2014 Oct 13. PubMed PMID: 25308930.

12: Cadoo KA, Gucalp A, Traina TA. Palbociclib: an evidence-based review of its potential in the treatment of breast cancer. Breast Cancer (Dove Med Press). 2014 Aug 4;6:123-33. doi: 10.2147/BCTT.S46725. eCollection 2014. Review. PubMed PMID: 25177151; PubMed Central PMCID: PMC4128689.

13: Pauls E, Badia R, Torres-Torronteras J, Ruiz A, Permanyer M, Riveira-Muñoz E, Clotet B, Marti R, Ballana E, Esté JA. Palbociclib, a selective inhibitor of cyclin-dependent kinase4/6, blocks HIV-1 reverse transcription through the control of sterile α motif and HD domain-containing protein-1 (SAMHD1) activity. AIDS. 2014 Sep 24;28(15):2213-22. doi: 10.1097/QAD.0000000000000399. PubMed PMID: 25036183.

14: Palbociclib ups PFS in HER2-/ER+ breast cancer. Cancer Discov. 2014 Jun;4(6):624-5. doi: 10.1158/2159-8290.CD-NB2014-053. Epub 2014 Apr 6. PubMed PMID: 24891344.

15: Rocca A, Farolfi A, Bravaccini S, Schirone A, Amadori D. Palbociclib (PD 0332991) : targeting the cell cycle machinery in breast cancer. Expert Opin Pharmacother. 2014 Feb;15(3):407-20. doi: 10.1517/14656566.2014.870555. Epub 2013 Dec 26. Review. PubMed PMID: 24369047.

EOS Med Chem produce EW-7197 1352608-82-2 in GMP plant, C-GMP standard, now COA, NMR, HPLC, MS is ok.

Name: EW-7197
CAS#: 1352608-82-2
Chemical Formula: C22H18FN7
Exact Mass: 399.1608
Molecular Weight: 399.4334
Elemental Analysis: C, 66.15; H, 4.54; F, 4.76; N, 24.55


EOS Med Chem produce EW-7197 1352608-82-2 in GMP plant, C-GMP standard, now COA, NMR, HPLC, MS is ok.

EW-7197 1352608-82-2 Intermediates, EOS Med Chem have 8; EW-7197 1352608-82-2 Impurity we have 10, all from GMP, FDA plant.
Now EW-7197 1352608-82-2 DMF document is preparing.
Until 2016, Aug, EW-7197 1352608-82-2 more than produced 25kg API, 120kg Intermediates

GMP PRODUCE:

Alectinib;Veliparib;Acalabrutinib;Venetoclax;Sotagliflozin;Ledipasvir;LX1606;Anacetrapib;Abemaciclib 

2016 Mumbai CPHI, Hope to meet!

2016 Barcelona CPHI, Hope to meet!

2016 Korea(한국) CPHI, C40, Welcome!

2016 Shanghai CPHI, W5C47, Welcome!

EOS Med Chem, Medchem is Big

執大象，天下往，往而無害，安平泰

網址: www.eosmedchem.com 

郵箱: gutian@eosmedchem.com; eosmedchem@gmail.com 

辦公室: 0086-531-69905422-806(直通)

攜帶番號 & WhatsApp: +8618653174435

Skype: willgutian

TEW-7197 Intermediates N-(5-iodopyridin-2-yl)-N,N-dimethylmethanediamine
TEW-7197 Intermediates 6-iodo-[1,2,4]triazolo[1,5-a]pyridine 614750-84-4
TEW-7197 Intermediates [1,2,4]triazolo[1,5-a]pyridine-6-carbaldehyde 614750-81-1
TEW-7197 Intermediates diphenyl ((6-methylpyridin-2-yl)(phenylamino)methyl)phosphonate 614750-85-5
TEW-7197 Intermediates 2-([1,2,4]triazolo[1,5-a]pyridin-6-yl)-1-(6-methylpyridin-2-yl)ethanone 614750-82-2
TEW-7197 Intermediates 1-([1,2,4]triazolo[1,5-a]pyridin-6-yl)-2-(6-methylpyridin-2-yl)ethane-1,2-dione 356560-84-4
TEW-7197 Intermediates 6-(2-(dimethoxymethyl)-5-(6-methylpyridin-2-yl)-1H-imidazol-4-yl)-[1,2,4]triazolo[1,5-a]pyridine 1352609-89-2
TEW-7197 Intermediates 4-([1,2,4]triazolo[1,5-a]pyridin-6-yl)-5-(6-methylpyridin-2-yl)-1H-imidazole-2-carbaldehyde 1352609-91-6


Description: TEW-7197, also known as EW-7197, is and orally bioavailable inhibitor of the serine/threonine kinase, transforming growth factor (TGF)-beta receptor type 1 (TGFBR1), also known as activin receptor-like kinase 5 (ALK5), with potential antineoplastic activity. Upon oral administration, TEW-7197 inhibits the activity of TGFBR1 and prevents TGF-beta/TGFBR1-mediated signaling. This suppresses tumor growth in TGFBR1-overexpressing tumor cells. TGFBR1, which is overexpressed in a variety of tumor cell types, plays a key role in tumor cell proliferation.
Synonym: TEW-7197; TEW 7197; TEW7197; EW-7197; EW 7197; EW7197.
IUPAC/Chemical Name: N-((4-([1,2,4]triazolo[1,5-a]pyridin-6-yl)-5-(6-methylpyridin-2-yl)-1H-imidazol-2-yl)methyl)-2-fluoroaniline
SMILES Code: FC1=CC=CC=C1NCC2=NC(C3=CN4C(C=C3)=NC=N4)=C(C5=NC(C)=CC=C5)N2

1: Kim MJ, Park SA, Kim CH, Park SY, Kim JS, Kim DK, Nam JS, Sheen YY. TGF-β Type I Receptor Kinase Inhibitor EW-7197 Suppresses Cholestatic Liver Fibrosis by Inhibiting HIF1α-Induced Epithelial Mesenchymal Transition. Cell Physiol Biochem. 2016;38(2):571-88. doi: 10.1159/000438651. PubMed PMID: 26845171.
2: Naka K, Ishihara K, Jomen Y, Jin CH, Kim DH, Gu YK, Jeong ES, Li S, Krause DS, Kim DW, Bae E, Takihara Y, Hirao A, Oshima H, Oshima M, Ooshima A, Sheen YY, Kim SJ, Kim DK. Novel oral transforming growth factor-β signaling inhibitor EW-7197 eradicates CML-initiating cells. Cancer Sci. 2016 Feb;107(2):140-8. doi: 10.1111/cas.12849. PubMed PMID: 26583567; PubMed Central PMCID: PMC4768399.
3: Park SA, Kim MJ, Park SY, Kim JS, Lim W, Nam JS, Yhong Sheen Y. TIMP-1 mediates TGF-β-dependent crosstalk between hepatic stellate and cancer cells via FAK signaling. Sci Rep. 2015 Nov 9;5:16492. doi: 10.1038/srep16492. PubMed PMID: 26549110; PubMed Central PMCID: PMC4637930.
4: Krishnaiah M, Jin CH, Sheen YY, Kim DK. Synthesis and biological evaluation of 5-(fluoro-substituted-6-methylpyridin-2-yl)-4-([1,2,4]triazolo[1,5-a]pyridin-6-yl )imidazoles as inhibitors of transforming growth factor-β type I receptor kinase. Bioorg Med Chem Lett. 2015 Nov 15;25(22):5228-31. doi: 10.1016/j.bmcl.2015.09.058. PubMed PMID: 26483198.
5: Park SY, Kim MJ, Park SA, Kim JS, Min KN, Kim DK, Lim W, Nam JS, Sheen YY. Combinatorial TGF-β attenuation with paclitaxel inhibits the epithelial-to-mesenchymal transition and breast cancer stem-like cells. Oncotarget. 2015 Nov 10;6(35):37526-43. doi: 10.18632/oncotarget.6063. PubMed PMID: 26462028; PubMed Central PMCID: PMC4741946.
6: Park SA, Kim MJ, Park SY, Kim JS, Lee SJ, Woo HA, Kim DK, Nam JS, Sheen YY. EW-7197 inhibits hepatic, renal, and pulmonary fibrosis by blocking TGF-β/Smad and ROS signaling. Cell Mol Life Sci. 2015 May;72(10):2023-39. doi: 10.1007/s00018-014-1798-6. PubMed PMID: 25487606.
7: Son JY, Park SY, Kim SJ, Lee SJ, Park SA, Kim MJ, Kim SW, Kim DK, Nam JS, Sheen YY. EW-7197, a novel ALK-5 kinase inhibitor, potently inhibits breast to lung metastasis. Mol Cancer Ther. 2014 Jul;13(7):1704-16. doi: 10.1158/1535-7163.MCT-13-0903. PubMed PMID: 24817629.
8: Jin CH, Krishnaiah M, Sreenu D, Subrahmanyam VB, Rao KS, Lee HJ, Park SJ, Park HJ, Lee K, Sheen YY, Kim DK. Discovery of N-((4-([1,2,4]triazolo[1,5-a]pyridin-6-yl)-5-(6-methylpyridin-2-yl)-1H-imidazol-2 -yl)methyl)-2-fluoroaniline (EW-7197): a highly potent, selective, and orally bioavailable inhibitor of TGF-β type I receptor kinase as cancer immunotherapeutic/antifibrotic agent. J Med Chem. 2014 May 22;57(10):4213-38. doi: 10.1021/jm500115w. PubMed PMID: 24786585.
9: Sheen YY, Kim MJ, Park SA, Park SY, Nam JS. Targeting the Transforming Growth Factor-β Signaling in Cancer Therapy. Biomol Ther (Seoul). 2013 Sep 30;21(5):323-31. doi: 10.4062/biomolther.2013.072. Review. PubMed PMID: 24244818; PubMed Central PMCID: PMC3825194.
10: Yoon JH, Jung SM, Park SH, Kato M, Yamashita T, Lee IK, Sudo K, Nakae S, Han JS, Kim OH, Oh BC, Sumida T, Kuroda M, Ju JH, Jung KC, Park SH, Kim DK, Mamura M. Activin receptor-like kinase5 inhibition suppresses mouse melanoma by ubiquitin degradation of Smad4, thereby derepressing eomesodermin in cytotoxic T lymphocytes. EMBO Mol Med. 2013 Nov;5(11):1720-39. doi: 10.1002/emmm.201302524. Erratum in: EMBO Mol Med. 2014 May;6(5):703. PubMed PMID: 24127404; PubMed Central PMCID: PMC3840488.

EOS Med Chem produce Brigatinib (AP-26113) 1197953-54-0 in GMP plant, C-GMP standard, now COA, NMR, HPLC, MS is ok.

Name: Brigatinib (AP-26113)
CAS#: 1197953-54-0
Chemical Formula: C29H39ClN7O2P
Exact Mass: 583.25914
Molecular Weight: 584.10176
Elemental Analysis: C, 59.63; H, 6.73; Cl, 6.07; N, 16.79; O, 5.48; P, 5.30

EOS Med Chem produce Brigatinib (AP-26113) 1197953-54-0 in GMP plant, C-GMP standard, now COA, NMR, HPLC, MS is ok.


Brigatinib (AP-26113) 1197953-54-0 Intermediates, EOS Med Chem have 8; Brigatinib (AP-26113) 1197953-54-0 Impurity we have 10, all from GMP, FDA plant.
Now Brigatinib (AP-26113) 1197953-54-0 DMF document is preparing.
Until 2016, Aug, Brigatinib (AP-26113) 1197953-54-0 more than produced 25kg API, 120kg Intermediates

Brigatinib AP-26113 ； 1197953-54-0
Brigatinib Intermediates (2-((2,5-dichloropyrimidin-4-yl)amino)phenyl)dimethylphosphine oxide 1197953-49-3


Description: Brigatinib, also known as AP-26113, is an orally active, potent and selective Dual ALK/EGFR inhibitor. AP26113 binds to and inhibits ALK kinase and ALK fusion proteins as well as EGFR and mutant forms. This leads to the inhibition of ALK kinase and EGFR kinase, disrupts their signaling pathways and eventually inhibits tumor cell growth in susceptible tumor cells. In addition, AP26113 appears to overcome mutation-based resistance. ALK belongs to the insulin receptor superfamily and plays an important role in nervous system development; ALK dysregulation and gene rearrangements are associated with a series of tumors. EGFR is overexpressed in a variety of cancer cell types.
Synonym: AP26113; AP-26113; AP 26113, Brigatinib
IUPAC/Chemical Name: (2-((5-chloro-2-((2-methoxy-4-(4-(4-methylpiperazin-1-yl)piperidin-1-yl)phenyl)amino)pyrimidin-4-yl)amino)phenyl)dimethylphosphine oxide
SMILES Code: CN1CCN(C2CCN(C3=CC=C(NC4=NC=C(Cl)C(NC5=CC=CC=C5P(C)(C)=O)=N4)C(OC)=C3)CC2)CC1


The following public resources have listed a wrong structure for Brigatinib (AP-26113)
1. Some papers:
Such as Onco Targets Ther. 2014 Mar 5;7:375-85., http://www.ncbi.nlm.nih.gov/pubmed/24623980.
2. Wikipedia (https://en.wikipedia.org/wiki/Brigatinib, last visited on 12/9/2015).
3. Sci-Finder Scholar Database: Before December 2015, Sci-Finder Scholar Database also wrongly listed CAS#1197958-12-5 as Brigatinib (AP26113). Now Sci-Finder Scholar Database has corrected.
4. Pubchem: https://pubchem.ncbi.nlm.nih.gov/compound/ap26113, last visited: 12/9/2015.
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--------------------------------------------------- More information related to AP26113 bioactivities---------------------------------------------
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AP26113 is a potent and selective ALK inhibitor. AP26113 induced tumor regression in BaF3 xenograft model expressing EML4-ALK, and EML4-ALK harboring G1269S and L1196M (gatekeeper) mutations. In preclinical studies, AP26113 was shown to be active against all 9 clinically-identified crizotinib-resistant mutants tested. AP26113 is also a potent, reversible inhibitor of activated and T790M-mutant EGFR, yet it does not inhibit the native enzyme [94]. A phase I/II study was initiated (NCT01449461) to evaluate AP26113 as a dual ALK/mutant EGFR inhibitor. As of 14 Jan 2013, 44 patients were enrolled including 37 with NSCLC. In the dose escalation phase (30-300 mg), two dose limiting toxicities were observed, grade 3 ALT elevations at 240 mg and grade 4 dyspnea at 300 mg. The recommended phase II dose was identified as 180 mg. The most common adverse effects were nausea (45%), fatigue (39%), diarrhea (27%). Among 18 evaluable ALK+ patients, four out of 5 patients with CNS lesions showed improvement on follow up imaging, including one patient resistant to crizotinib and ceritinib. Sixteen patients had EGFR mutation (EGFRm). Of 12 patients with EGFRm, one patient responded at 120 mg (duration 21 weeks, ongoing) and 6 patients had stable disease (2 ongoing, duration 7 and 31 weeks, respectively). In a later update, 114 pts were enrolled: 65 in phase 1 (30–300 mg) and 49 in phase 2 (180 mg) [93]. There were 106 pts with NSCLC. The most common treatment-emergent AEs (20%) were similar to the previous report. Early onset of pulmonary symptoms (dyspnea with hypoxia and/or findings on imaging) were observed in 6/45 (13%) pts at 180 mg QD. These symptoms needed urgent intervention. The respiratory symptoms were not observed at 90 mg QD (n = 8) or in the lead-in dose cohort (n = 19; initiated at 90 mg QD, escalated to 180 mg QD after 1 wk). Therefore, further enrollment with this dose escalation scheme, and an additional cohort of 90 mg QD without escalation were being added. Among 38 evaluable ALK+ NSCLC pts who had prior crizotinib, 24 (63%) reported response, including one CR. Six of 10 pts enrolled with untreated or progressing brain metastases showed response in brain, including 4 with complete resolution; 2 stable disease, 2 progressed; AP26113 has promising anti-tumor activity in pts with crizotinib-resistant ALK+ NSCLC, including pts with brain metastases. A randomized phase 2 trial of AP26113 comparing 90 mg QD vs. 90 mg QD escalating to 180 mg QD in crizotinib-resistant ALK+ NSCLC was planned. (copied from http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4349797/)


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12: Ceccon M, Mologni L, Giudici G, Piazza R, Pirola A, Fontana D, Gambacorti-Passerini C. Treatment Efficacy and Resistance Mechanisms Using the Second-Generation ALK Inhibitor AP26113 in Human NPM-ALK-Positive Anaplastic Large Cell Lymphoma. Mol Cancer Res. 2015 Apr;13(4):775-83. doi: 10.1158/1541-7786.MCR-14-0157. Epub 2014 Nov 24. PubMed PMID: 25421750.
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Name: Alectinib HCl 
CAS#: 1256589-74-8 (HCl) 
Chemical Formula: C30H35ClN4O2 
Exact Mass: 
Molecular Weight: 519.086 
Elemental Analysis: C, 69.42; H, 6.80; Cl, 6.83; N, 10.79; O, 6.16


EOS Med Chem produce Alectinib,AF 802, CH 5424802, RO 5424802, Alecensa, 1256589-74-8  in GMP plant, C-GMP standard, now COA, NMR, HPLC, MS is ok.
Alectinib,AF 802, CH 5424802, RO 5424802, Alecensa, 1256589-74-8  Intermediates, EOS Med Chem have 8; Alectinib,AF 802, CH 5424802, RO 5424802, Alecensa, 1256589-74-8  Impurity we have 10, all from GMP, FDA plant.


Now Alectinib,AF 802, CH 5424802, RO 5424802, Alecensa, 1256589-74-8  DMF document is preparing.
Until 2016, Aug, Alectinib,AF 802, CH 5424802, RO 5424802, Alecensa, 1256589-74-8  more than produced 25kg API, 120kg Intermediates

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Alectinib;Veliparib;Acalabrutinib;Venetoclax;Sotagliflozin;Ledipasvir;LX1606;Anacetrapib;Abemaciclib 

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Alectinib Alecensa;RG-7853; RO-5424802; AF-802; CH-5424802 1256580-46-7(free base)
Alectinib Alecensa;RG-7853; RO-5424802; AF-802; CH-5424802 1256589-74-8(HCl)
Alectinib Intermediates Ethyl 2-(4-bromophenyl)-2-methylpropanoate 32454-36-7
Alectinib Intermediates 2-(4-bromophenyl)-2-methylpropanoic acid 32454-35-6
Alectinib Intermediates 2-methyl-2-(4-vinylphenyl)propanoic acid 1256584-72-1
Alectinib Intermediates 2-(4-ethylphenyl)-2-methylpropanoic acid 1247119-83-0
Alectinib Intermediates 2-(4-ethyl-3-iodophenyl)-2-methylpropanoic acid 1256584-73-2
Alectinib Intermediates Tert-butyl 4-(4-ethyl-3-iodophenyl)-4-methyl-3-oxopentanoate 1256584-74-3
Alectinib Intermediates Tert-butyl 6-cyano-2-(2-(4-ethyl-3-iodophenyl)propan-2-yl)-1H-indole-3-carboxylate 1256585-29-1
Alectinib Intermediates 6-cyano-2-(2-(4-ethyl-3-(4-morpholinopiperidin-1-yl)phenyl)propan-2-yl)-1H-indole-3-carboxylic acid 1256584-78-7




Description: Alectinib, also known as AF802, or CH5424802 or RO5424802, is a potent, selective, and orally available ALK inhibitor with a unique chemical scaffold, showing preferential antitumor activity against cancers with gene alterations of ALK, such as nonsmall cell lung cancer (NSCLC) cells expressing EML4-ALK fusion and anaplastic large-cell lymphoma (ALCL) cells expressing NPM-ALK fusion in vitro and in vivo. Alectinib inhibited ALK L1196M, which corresponds to the gatekeeper mutation conferring common resistance to kinase inhibitors, and blocked EML4-ALK L1196M-driven cell growth. Alectinib (as HCl salt) was approved in Dec. 2015.
Synonym: AF 802; AF-802; AF802; CH5424802; CH5424802; CH 5424802; RO5424802; RO 5424802; RO5424802, Alectinib; brand name: Alecensa
IUPAC/Chemical Name: 9-ethyl-6,6-dimethyl-8-(4-morpholinopiperidin-1-yl)-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile hydrochloride
SMILES Code: N#CC1=CC2=C(C=C1)C3=C(C(C)(C)C4=CC(N5CCC(N6CCOCC6)CC5)=C(CC)C=C4C3=O)N2.[H]Cl

Related CAS# 
CAS#1256580-46-7 (Alectinib free base) 
CAS#1256589-74-8 (Alectinib HCl)

1: Ou SH, Weitz M, Jalas JR, Kelly DF, Wong V, Azada MC, Quines O, Klempner SJ. Alectinib induced CNS radiation necrosis in an ALK+NSCLC patient with a remote (7 years) history of brain radiation. Lung Cancer. 2016 Jun;96:15-8. doi: 10.1016/j.lungcan.2016.03.008. Epub 2016 Mar 26. PubMed PMID: 27133743.
2: Tchekmedyian N, Ali SM, Miller VA, Haura EB. Acquired ALK L1152R Mutation Confers Resistance to Ceritinib and Predicts Response to Alectinib. J Thorac Oncol. 2016 Apr 15. pii: S1556-0864(16)30081-8. doi: 10.1016/j.jtho.2016.03.018. [Epub ahead of print] PubMed PMID: 27091190.
3: Aikawa H, Hayashi M, Ryu S, Yamashita M, Ohtsuka N, Nishidate M, Fujiwara Y, Hamada A. Visualizing spatial distribution of alectinib in murine brain using quantitative mass spectrometry imaging. Sci Rep. 2016 Mar 30;6:23749. doi: 10.1038/srep23749. PubMed PMID: 27026287; PubMed Central PMCID: PMC4812395.
4: Dong X, Fernandez-Salas E, Li E, Wang S. Elucidation of Resistance Mechanisms to Second-Generation ALK Inhibitors Alectinib and Ceritinib in Non-Small Cell Lung Cancer Cells. Neoplasia. 2016 Mar;18(3):162-71. doi: 10.1016/j.neo.2016.02.001. PubMed PMID: 26992917; PubMed Central PMCID: PMC4796802.
5: Tanaka H, Taima K, Morimoto T, Nakamura K, Tanaka Y, Itoga M, Takanashi S, Okumura K. Dramatic response to alectinib in a patient of ALK-rearranged lung cancer with poor performance status. BMC Res Notes. 2016 Mar 17;9(1):173. doi: 10.1186/s13104-016-1983-9. PubMed PMID: 26987388; PubMed Central PMCID: PMC4794901.
6: Yoshida T, Hida T, Yatabe Y. Rapid and dramatic response to alectinib in an ALK rearranged non-small-cell lung cancer patient who are critically ill. Anticancer Drugs. 2016 Mar 2. [Epub ahead of print] PubMed PMID: 26938871.
7: Yoshimura Y, Kurasawa M, Yorozu K, Puig O, Bordogna W, Harada N. Antitumor activity of alectinib, a selective ALK inhibitor, in an ALK-positive NSCLC cell line harboring G1269A mutation : Efficacy of alectinib against ALK G1269A mutated cells. Cancer Chemother Pharmacol. 2016 Mar;77(3):623-8. doi: 10.1007/s00280-016-2977-y. Epub 2016 Feb 5. PubMed PMID: 26849637.
8: Gainor JF, Chi AS, Logan J, Hu R, Oh KS, Brastianos PK, Shih HA, Shaw AT. Alectinib Dose Escalation Reinduces Central Nervous System Responses in Patients with Anaplastic Lymphoma Kinase-Positive Non-Small Cell Lung Cancer Relapsing on Standard Dose Alectinib. J Thorac Oncol. 2016 Feb;11(2):256-60. doi: 10.1016/j.jtho.2015.10.010. Epub 2015 Dec 18. PubMed PMID: 26845119; PubMed Central PMCID: PMC4743545.
9: Takegawa N, Hayashi H, Iizuka N, Takahama T, Ueda H, Tanaka K, Takeda M, Nakagawa K. Transformation of ALK rearrangement-positive adenocarcinoma to small-cell lung cancer in association with acquired resistance to alectinib. Ann Oncol. 2016 May;27(5):953-5. doi: 10.1093/annonc/mdw032. Epub 2016 Jan 24. PubMed PMID: 26811347.
10: Pirker R, Filipits M. Alectinib in RET-rearranged non-small cell lung cancer-Another progress in precision medicine? Transl Lung Cancer Res. 2015 Dec;4(6):797-800. doi: 10.3978/j.issn.2218-6751.2015.03.08. PubMed PMID: 26798590; PubMed Central PMCID: PMC4700226.
11: Fujita S, Masago K, Katakami N, Yatabe Y. Transformation to SCLC after Treatment with the ALK Inhibitor Alectinib. J Thorac Oncol. 2016 Jan 2. pii: S1556-0864(15)00275-0. doi: 10.1016/j.jtho.2015.12.105. [Epub ahead of print] PubMed PMID: 26751586.
12: Alectinib Approved for ALK+ Lung Cancer. Cancer Discov. 2016 Feb;6(2):115. doi: 10.1158/2159-8290.CD-NB2016-001. Epub 2016 Jan 6. PubMed PMID: 26739884.
13: Isozaki H, Ichihara E, Takigawa N, Ohashi K, Ochi N, Yasugi M, Ninomiya T, Yamane H, Hotta K, Sakai K, Matsumoto K, Hosokawa S, Bessho A, Sendo T, Tanimoto M, Kiura K. Non-Small Cell Lung Cancer Cells Acquire Resistance to the ALK Inhibitor Alectinib by Activating Alternative Receptor Tyrosine Kinases. Cancer Res. 2016 Mar 15;76(6):1506-16. doi: 10.1158/0008-5472.CAN-15-1010. Epub 2015 Dec 30. PubMed PMID: 26719536.
14: Shaw AT, Gandhi L, Gadgeel S, Riely GJ, Cetnar J, West H, Camidge DR, Socinski MA, Chiappori A, Mekhail T, Chao BH, Borghaei H, Gold KA, Zeaiter A, Bordogna W, Balas B, Puig O, Henschel V, Ou SH; study investigators. Alectinib in ALK-positive, crizotinib-resistant, non-small-cell lung cancer: a single-group, multicentre, phase 2 trial. Lancet Oncol. 2016 Feb;17(2):234-42. doi: 10.1016/S1470-2045(15)00488-X. Epub 2015 Dec 19. PubMed PMID: 26708155; PubMed Central PMCID: PMC4752892.
15: Jassem J. Alectinib in crizotinib-resistant, ALK-positive NSCLC. Lancet Oncol. 2016 Feb;17(2):134-5. doi: 10.1016/S1470-2045(15)00555-0. Epub 2015 Dec 19. PubMed PMID: 26708154.
16: Tani T, Yasuda H, Hamamoto J, Kuroda A, Arai D, Ishioka K, Ohgino K, Miyawaki M, Kawada I, Naoki K, Hayashi Y, Betsuyaku T, Soejima K. Activation of EGFR Bypass Signaling by TGFα Overexpression Induces Acquired Resistance to Alectinib in ALK-Translocated Lung Cancer Cells. Mol Cancer Ther. 2016 Jan;15(1):162-71. doi: 10.1158/1535-7163.MCT-15-0084. Epub 2015 Dec 18. PubMed PMID: 26682573.
17: Miyamoto S, Ikushima S, Ono R, Awano N, Kondo K, Furuhata Y, Fukumoto K, Kumasaka T. Transformation to small-cell lung cancer as a mechanism of acquired resistance to crizotinib and alectinib. Jpn J Clin Oncol. 2016 Feb;46(2):170-3. doi: 10.1093/jjco/hyv173. Epub 2015 Nov 27. PubMed PMID: 26613679.
18: Ou SH, Ahn JS, De Petris L, Govindan R, Yang JC, Hughes B, Lena H, Moro-Sibilot D, Bearz A, Ramirez SV, Mekhail T, Spira A, Bordogna W, Balas B, Morcos PN, Monnet A, Zeaiter A, Kim DW. Alectinib in Crizotinib-Refractory ALK-Rearranged Non-Small-Cell Lung Cancer: A Phase II Global Study. J Clin Oncol. 2016 Mar 1;34(7):661-8. doi: 10.1200/JCO.2015.63.9443. Epub 2015 Nov 23. PubMed PMID: 26598747.
19: Song Z, Wang M, Zhang A. Alectinib: a novel second generation anaplastic lymphoma kinase (ALK) inhibitor for overcoming clinically-acquired resistance. Acta Pharm Sin B. 2015 Jan;5(1):34-7. doi: 10.1016/j.apsb.2014.12.007. Epub 2015 Jan 24. Review. PubMed PMID: 26579422; PubMed Central PMCID: PMC4629211.
20: Takeuchi K, Togashi Y, Kamihara Y, Fukuyama T, Yoshioka H, Inoue A, Katsuki H, Kiura K, Nakagawa K, Seto T, Maemondo M, Hida T, Harada M, Ohe Y, Nogami N, Yamamoto N, Nishio M, Tamura T. Prospective and clinical validation of ALK immunohistochemistry: results from the phase I/II study of alectinib for ALK-positive lung cancer (AF-001JP study). Ann Oncol. 2016 Jan;27(1):185-92. doi: 10.1093/annonc/mdv501. Epub 2015 Oct 20. PubMed PMID: 26487585; PubMed Central PMCID: PMC4684157.