NMR,HPLC, LCMS, COA, Pls check:
Description: AZD3965 is a selective inhibitor of monocarboxylate transporter 1 (MCT1) with a binding affinity of 1.6 nM, is 6 fold selective over MCT2 and does not inhibit MCT4 at 10 μM. In vivo, AZD3965 is well tolerated and induces a dose and time dependent accumulation of lactate in the tumours, suppresses tumour growth and in the Raji model potentiates the effects of Rituxan, doxorubicin and bendamustine. The selective inhibition of lactate transport by the MCT1 inhibitor AZD3965 offers an novel mechanism for targeting the metabolic phenotype in tumours that preferentially express MCT1.
Name: AZD-3965
CAS#: 1448671-31-5 (or 733809-45-5)
Chemical Formula: C21H24F3N5O5S
Exact Mass: 515.14502
Molecular Weight: 515.50597
Elemental Analysis: C, 48.93; H, 4.69; F, 11.06; N, 13.59; O, 15.52; S, 6.22
Synonym: AZD3965; AZD-3965; AZD 3965.
IUPAC/Chemical Name: (S)-5-(4-hydroxy-4-methylisoxazolidine-2-carbonyl)-1-isopropyl-3-methyl-6-((3-methyl-5-(trifluoromethyl)-1H-pyrazol-4-yl)methyl)thieno[2,3-d]pyrimidine-2,4(1H,3H)-dione
InChi Key: PRNXOFBDXNTIFG-FQEVSTJZSA-N
InChi Code: InChI=1S/C21H24F3N5O5S/c1-9(2)29-18-14(16(30)27(5)19(29)32)13(17(31)28-7-20(4,33)8-34-28)12(35-18)6-11-10(3)25-26-15(11)21(22,23)24/h9,33H,6-8H2,1-5H3,(H,25,26)/t20-/m0/s1
SMILES Code: O=C1N(C(C)C)C2=C(C(C(N3OC[C@@](C)(O)C3)=O)=C(CC4=C(C(F)(F)F)NN=C4C)S2)C(N1C)=O
TECHNICAL DATA
Appearance: White to off-white solid powder
Purity: >98% (or refer to the Certificate of Analysis)
Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility: Soluble in DMSO, not in water
Shelf Life: >2 years if stored properly
Drug Formulation: This drug may be formulated in DMSO
Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).
2017 China CPHI: E1M35
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ADDITIONAL INFORMATION
AZD3965 sensitivity varied in vitro and was highest in hypoxia. Resistance in hypoxia was associated with increased MCT4 expression. In vivo, AZD3965 reduced tumor growth and increased intra-tumor lactate. In the tissue microarray, high MCT1 expression was associated with worse prognosis (p=0.014). MCT1 and hypoxia marker CA IX expression in the absence of MCT4 was observed in 21% of SCLC tumor
REFERENCES
1: Blackhall F. O11.5Activity of the monocarboxylate transporter 1 inhibitor AZD3965 in small cell lung cancer. Ann Oncol. 2015 Mar;26 Suppl 2:ii15. doi: 10.1093/annonc/mdv089.5. PubMed PMID: 25795820.
2: Lamb R, Harrison H, Hulit J, Smith DL, Lisanti MP, Sotgia F. Mitochondria as new therapeutic targets for eradicating cancer stem cells: Quantitative proteomics and functional validation via MCT1/2 inhibition. Oncotarget. 2014 Nov 30;5(22):11029-37. PubMed PMID: 25415228; PubMed Central PMCID: PMC4294326.
3: Marchiq I, Le Floch R, Roux D, Simon MP, Pouyssegur J. Genetic disruption of lactate/H+ symporters (MCTs) and their subunit CD147/BASIGIN sensitizes glycolytic tumor cells to phenformin. Cancer Res. 2015 Jan 1;75(1):171-80. doi: 10.1158/0008-5472.CAN-14-2260. Epub 2014 Nov 17. PubMed PMID: 25403912.
4: Bola BM, Chadwick AL, Michopoulos F, Blount KG, Telfer BA, Williams KJ, Smith PD, Critchlow SE, Stratford IJ. Inhibition of monocarboxylate transporter-1 (MCT1) by AZD3965 enhances radiosensitivity by reducing lactate transport. Mol Cancer Ther. 2014 Dec;13(12):2805-16. doi: 10.1158/1535-7163.MCT-13-1091. Epub 2014 Oct 3. PubMed PMID: 25281618; PubMed Central PMCID: PMC4258406.
5: Polański R, Hodgkinson CL, Fusi A, Nonaka D, Priest L, Kelly P, Trapani F, Bishop PW, White A, Critchlow SE, Smith PD, Blackhall F, Dive C, Morrow CJ. Activity of the monocarboxylate transporter 1 inhibitor AZD3965 in small cell lung cancer. Clin Cancer Res. 2014 Feb 15;20(4):926-37. doi: 10.1158/1078-0432.CCR-13-2270. Epub 2013 Nov 25. PubMed PMID: 24277449; PubMed Central PMCID: PMC3929348.
