Biggest LOXO-292, 2222755-14-6 supplier, LOXO-292, stock 210g, world biggest supplier.
LOXO-292, stock 210g, HPLC 99.8%, HNMR, COA, MSDS is ok.
This is only for R&D use, can not use in human, animal.
We have started researching the LOXO-292, 2222755-14-6 since 2018. We have already carried out batch production, also have completed the development of quality standards and process validation. The stable process is the guarantee of product quality. For these two products, we use HPLC-UV detection instead of other companies' HPLC-ELSD test, Our detection method is more sensitive.
LOXO-292 (ARRY-192) is an oral and selective investigational drug in clinical development for the treatment of patients with cancers that harbor abnormalities in the rearranged during transfection (RET) kinase.
LOXO-292, stock 210g, HPLC 99.8%, HNMR, COA, MSDS is ok.
This is only for R&D use, can not use in human, animal.
We have started researching the LOXO-292, 2222755-14-6 since 2018. We have already carried out batch production, also have completed the development of quality standards and process validation. The stable process is the guarantee of product quality. For these two products, we use HPLC-UV detection instead of other companies' HPLC-ELSD test, Our detection method is more sensitive.
LOXO-292 (ARRY-192) is an oral and selective investigational drug in clinical development for the treatment of patients with cancers that harbor abnormalities in the rearranged during transfection (RET) kinase.
FDA New, GMP Do
Clinical Phase II, III Intermediates
GMP Custom synthesis, Full Document
R&D Center: 8000 sq, More than 100 hoods
Pilot Plant: 20000sq, 40 reactors from 5-200L
Manufacturing Site: 800000sq, 40 reactors from 100-5000L
Name: LOXO-292
CAS#: 2222755-14-6
Chemical Formula: C29H31N9O3
Exact Mass: 553.255
Molecular Weight: 553.627
Elemental Analysis: C, 62.92; H, 5.64; N, 22.77; O, 8.67
Synonym: LOXO-292; LOXO292; LOXO 292; ARRY-192; ARRY192; ARRY 192
IUPAC/Chemical Name: 4-(5-(6-((6-methoxypyridin-3-yl)methyl)-3,6-diazabicyclo[3.1.1]heptan-3-yl)pyrazin-2-yl)-6-(((R)-morpholin-2-yl)methoxy)pyrazolo[1,5-a]pyridine-3-carbonitrile
InChi Key: GTQISTQEBXXLPC-UBVWURDFSA-N
InChi Code: InChI=1S/C29H31N9O3/c1-39-28-3-2-19(9-34-28)14-37-21-6-22(37)16-36(15-21)27-13-32-26(12-33-27)25-7-23(41-18-24-11-31-4-5-40-24)17-38-29(25)20(8-30)10-35-38/h2-3,7,9-10,12-13,17,21-22,24,31H,4-6,11,14-16,18H2,1H3/t21?,22?,24-/m1/s1
SMILES Code: N#CC1=C2C(C3=NC=C(N4CC(C5)N(CC6=CC=C(OC)N=C6)C5C4)N=C3)=CC(OC[C@H]7CNCCO7)=CN2N=C1
TECHNICAL DATA
Appearance: 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
Shelf Life: >3 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).
Harmonized System Code: 2934990300
REFERENCES
A Phase 1/2 Study of Oral LOXO-292 in Patients With Advanced Solid Tumors, Including RET Fusion-Positive Solid Tumors, Medullary Thyroid Cancer, and Other Tumors With RET Activation (LIBRETTO-001) https://clinicaltrials.gov/ct2/show/NCT03157128?term=loxo-292&rank=1
LOXO-292 is an oral and selective investigational drug in clinical development for the treatment of patients with cancers that harbor abnormalities in the rearranged during transfection (RET) kinase. Genomic alterations in the RET kinase, which include fusions and activating point mutations, lead to overactive RET signaling and uncontrolled cell growth. RET fusions have been identified in approximately 2% of non-small cell lung cancer, 10-20% of papillary thyroid cancers, and a subset of other cancers. Activating RET point mutations account for approximately 60% of medullary thyroid cancer (MTC).
Both RET fusion cancers and RET-mutant MTC are primarily dependent on a single activated kinase for their proliferation and survival. This dependency, often referred to as “oncogene addiction,” renders such tumors highly susceptible to small molecule inhibitors targeting RET. LOXO-292 was designed to inhibit native RET signaling as well as anticipated acquired resistance mechanisms that could otherwise limit the activity of this therapeutic approach.
LOXO-292 is currently being studied in the global LIBRETTO-001 Phase 1/2 trial.
Updated interim clinical data for LOXO-292 from the global Phase 1/2 LIBRETTO-001 trial in patients with RET fusion-positive non-small cell lung cancer (NSCLC) were presented at the 2018 IASLC World Conference on Lung Cancer and in patients with RET-mutant medullary thyroid cancer (MTC) and RET fusion-positive thyroid cancer at the 2018 Annual Meeting of the American Thyroid Association (ATA). Read the presentation from the IASLC World Conference on Lung Cancer here and the presentation from ATA here.
RET fusion-positive NSCLC
The data presented were based on a July 19, 2018 data cut-off date and included the 38 patients with RET fusion-positive NSCLC who were initially included in the LOXO-292 presentation at the 2018 American Society of Clinical Oncology (ASCO) Annual Meeting.
Patients were heavily pretreated, having received a median of three prior systemic treatment regimens. Thirty-nine percent had received both prior platinum-based chemotherapy and an anti-PD-1 or anti-PD-L1 therapy.
With 3.5 months of additional follow-up since the 2018 ASCO Annual Meeting presentation, LOXO-292 demonstrated encouraging, early evidence of durable activity, with 25 of 26 (96%) responding RET fusion-positive NSCLC patients remaining on therapy and 24 of 26 (92%) with responses ongoing (median follow-up of 8.5 months for all 38 patients; median follow-up of 9.5 months for responding patients). The longest responding patient on therapy was the first RET fusion-positive NSCLC patient enrolled, who had been on therapy for more than 14 months as of the data cut-off date.
The new data cutoff date allowed for the inclusion of first follow-up scans for eight patients who had not had any post-baseline response assessment as of the ASCO presentation. Of 38 patients with RET fusion-positive NSCLC, 26 demonstrated an objective response by RECIST 1.1 (all partial responses, including one patient with an unconfirmed partial response awaiting a confirmatory response assessment) and six additional patients demonstrated evidence of tumor regression (-3% to -29%). The overall response rate was 68% (26/38) (95% CI: 51%-83%) and the confirmed overall response rate was 68% (25/37) (95% CI: 50%-82%). Response assessments were performed by the local clinical trial sites.
Anti-tumor activity was observed regardless of RET fusion partner (including KIF5B) and prior treatment, including chemotherapy, immunotherapy and multikinase inhibitors. Four patients had RECIST target lesions in the central nervous system (CNS) and all four exhibited confirmed intracranial responses by RECIST 1.1 (one complete response, three partial responses).
RET-mutant MTC and RET fusion-positive thyroid cancer
The data presented were based on a July 19, 2018 data cut-off date and included the 29 patients with RET-mutant MTC and the nine patients with RET fusion-positive thyroid cancer who were initially included in the LOXO-292 presentation at the 2018 ASCO Annual Meeting.
Patients were heavily pretreated, having received a median of three prior systemic treatment regimens. Of the patients with RET-mutant MTC, 79% (23/29) had previously received cabozantinib or vandetanib and 45% (13/29) had received prior treatment with both agents. Of the patients with RET fusion-positive thyroid cancer, 78% (7/9) had previously received radioactive iodine and 78% (7/9) had previously received sorafenib or lenvatinib.
With 3.5 months of additional follow-up since the 2018 ASCO Annual Meeting presentation, LOXO-292 demonstrated encouraging, early evidence of durable activity. Sixteen of 17 (94%) responding RET-mutant MTC patients remained on therapy and in response (median follow-up of 7.6 months for all 29 patients; median follow-up of 8.4 months for responding patients). Seven of seven (100%) responding RET fusion-positive thyroid remained on therapy and in response (median follow-up of 7.6 months for all nine patients; median follow-up of 8.5 months for responding patients). The longest treated patient was the first RET-mutant MTC patient enrolled, who had been on therapy for more than 13 months as of the data cut-off date.
The new data cutoff date allowed for the inclusion of first follow-up scans for nine patients (seven with RET-mutant MTC and two with RET fusion-positive thyroid cancer) who had not had any post-baseline response assessment as of the ASCO presentation. Of 29 patients with RET-mutant MTC, 17 demonstrated an objective response by RECIST 1.1 (two complete responses and 15 partial responses, including two patients with unconfirmed partial responses awaiting confirmatory response assessments) and seven additional patients demonstrated evidence of tumor regression (-12% to -26%). The overall response rate was 59% (17/29) (95% CI: 39%-77%) and the confirmed overall response rate was 56% (15/27) (95% CI: 35%-75%). Included in this analysis are two patients with non-measurable disease at baseline (1 confirmed complete response, 1 stable disease). Of nine patients with RET fusion-positive thyroid cancer, seven demonstrated an objective response by RECIST 1.1 (all partial responses) and one additional patient demonstrated evidence of tumor regression (-21%). The confirmed overall response rate was 78% (7/9) (95% CI: 40%-97%). Included in the analysis is one patient with non-measurable disease at baseline (stable disease). Response assessments were performed by the local clinical trial sites.
Anti-tumor activity was observed regardless of RET mutation, RET fusion partner, and prior multikinase inhibitor treatment. One patient, with RET fusion-positive thyroid cancer, had RECIST target lesions in the central nervous system (CNS) and exhibited an intracranial partial response by RECIST 1.1, pending confirmation.
Overall safety analysis
Of the 82 patients in the safety analysis, most treatment-emergent adverse events were Grade 1 in severity and judged by the investigator as not related to LOXO-292. The treatment-emergent adverse events observed in ≥10% of patients, regardless of relationship to LOXO-292, were diarrhea (15% Grade 1, 7% Grade 2, 1% Grade 3), fatigue (9% Grade 1, 13% Grade 2, 0% ≥Grade 3), dry mouth (21% Grade 1, 0% ≥Grade 2), constipation (17% Grade 1, 2% Grade 2, 0% ≥Grade 3), hypomagnesemia (12% Grade 1, 1% Grade 2, 0% ≥Grade 3), cough (11% Grade 1, 1% Grade 2, 0% ≥Grade 3), headache (10% Grade 1, 1% Grade 2, 1% Grade 3) and nausea (9% Grade 1, 4% Grade 2, 0% ≥Grade 3). Four patients experienced adverse events ≥Grade 3 that were attributed to LOXO-292 (all Grade 3): tumor lysis syndrome, increased ALT/AST, diarrhea, and thrombocytopenia. All resolved with dose interruption. 160mg BID has been advanced as the Phase 2 dose, with dose exploration at 200mg BID ongoing to further characterize LOXO-292 safety and efficacy.
Interim clinical data were first presented at the 2018 ASCO Annual Meeting. Read the presentation from ASCO here.
Preclinical and clinical proof-of-concept data were also published in Annals of Oncology. That manuscript can be found here.
Preclinical data on the Loxo Oncology RET program were previously presented at the 2015 and 2016 AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics meetings. Those posters can be found here.
LOXO-292 is an oral and selective investigational drug in clinical development for the treatment of patients with cancers that harbor abnormalities in the rearranged during transfection (RET) kinase. Genomic alterations in the RET kinase, which include fusions and activating point mutations, lead to overactive RET signaling and uncontrolled cell growth. RET fusions have been identified in approximately 2% of non-small cell lung cancer, 10-20% of papillary thyroid cancers, and a subset of other cancers. Activating RET point mutations account for approximately 60% of medullary thyroid cancer (MTC).
Both RET fusion cancers and RET-mutant MTC are primarily dependent on a single activated kinase for their proliferation and survival. This dependency, often referred to as “oncogene addiction,” renders such tumors highly susceptible to small molecule inhibitors targeting RET. LOXO-292 was designed to inhibit native RET signaling as well as anticipated acquired resistance mechanisms that could otherwise limit the activity of this therapeutic approach.
LOXO-292 is currently being studied in the global LIBRETTO-001 Phase 1/2 trial.
Updated interim clinical data for LOXO-292 from the global Phase 1/2 LIBRETTO-001 trial in patients with RET fusion-positive non-small cell lung cancer (NSCLC) were presented at the 2018 IASLC World Conference on Lung Cancer and in patients with RET-mutant medullary thyroid cancer (MTC) and RET fusion-positive thyroid cancer at the 2018 Annual Meeting of the American Thyroid Association (ATA). Read the presentation from the IASLC World Conference on Lung Cancer here and the presentation from ATA here.
RET fusion-positive NSCLC
The data presented were based on a July 19, 2018 data cut-off date and included the 38 patients with RET fusion-positive NSCLC who were initially included in the LOXO-292 presentation at the 2018 American Society of Clinical Oncology (ASCO) Annual Meeting.
Patients were heavily pretreated, having received a median of three prior systemic treatment regimens. Thirty-nine percent had received both prior platinum-based chemotherapy and an anti-PD-1 or anti-PD-L1 therapy.
With 3.5 months of additional follow-up since the 2018 ASCO Annual Meeting presentation, LOXO-292 demonstrated encouraging, early evidence of durable activity, with 25 of 26 (96%) responding RET fusion-positive NSCLC patients remaining on therapy and 24 of 26 (92%) with responses ongoing (median follow-up of 8.5 months for all 38 patients; median follow-up of 9.5 months for responding patients). The longest responding patient on therapy was the first RET fusion-positive NSCLC patient enrolled, who had been on therapy for more than 14 months as of the data cut-off date.
The new data cutoff date allowed for the inclusion of first follow-up scans for eight patients who had not had any post-baseline response assessment as of the ASCO presentation. Of 38 patients with RET fusion-positive NSCLC, 26 demonstrated an objective response by RECIST 1.1 (all partial responses, including one patient with an unconfirmed partial response awaiting a confirmatory response assessment) and six additional patients demonstrated evidence of tumor regression (-3% to -29%). The overall response rate was 68% (26/38) (95% CI: 51%-83%) and the confirmed overall response rate was 68% (25/37) (95% CI: 50%-82%). Response assessments were performed by the local clinical trial sites.
Anti-tumor activity was observed regardless of RET fusion partner (including KIF5B) and prior treatment, including chemotherapy, immunotherapy and multikinase inhibitors. Four patients had RECIST target lesions in the central nervous system (CNS) and all four exhibited confirmed intracranial responses by RECIST 1.1 (one complete response, three partial responses).
RET-mutant MTC and RET fusion-positive thyroid cancer
The data presented were based on a July 19, 2018 data cut-off date and included the 29 patients with RET-mutant MTC and the nine patients with RET fusion-positive thyroid cancer who were initially included in the LOXO-292 presentation at the 2018 ASCO Annual Meeting.
Patients were heavily pretreated, having received a median of three prior systemic treatment regimens. Of the patients with RET-mutant MTC, 79% (23/29) had previously received cabozantinib or vandetanib and 45% (13/29) had received prior treatment with both agents. Of the patients with RET fusion-positive thyroid cancer, 78% (7/9) had previously received radioactive iodine and 78% (7/9) had previously received sorafenib or lenvatinib.
With 3.5 months of additional follow-up since the 2018 ASCO Annual Meeting presentation, LOXO-292 demonstrated encouraging, early evidence of durable activity. Sixteen of 17 (94%) responding RET-mutant MTC patients remained on therapy and in response (median follow-up of 7.6 months for all 29 patients; median follow-up of 8.4 months for responding patients). Seven of seven (100%) responding RET fusion-positive thyroid remained on therapy and in response (median follow-up of 7.6 months for all nine patients; median follow-up of 8.5 months for responding patients). The longest treated patient was the first RET-mutant MTC patient enrolled, who had been on therapy for more than 13 months as of the data cut-off date.
The new data cutoff date allowed for the inclusion of first follow-up scans for nine patients (seven with RET-mutant MTC and two with RET fusion-positive thyroid cancer) who had not had any post-baseline response assessment as of the ASCO presentation. Of 29 patients with RET-mutant MTC, 17 demonstrated an objective response by RECIST 1.1 (two complete responses and 15 partial responses, including two patients with unconfirmed partial responses awaiting confirmatory response assessments) and seven additional patients demonstrated evidence of tumor regression (-12% to -26%). The overall response rate was 59% (17/29) (95% CI: 39%-77%) and the confirmed overall response rate was 56% (15/27) (95% CI: 35%-75%). Included in this analysis are two patients with non-measurable disease at baseline (1 confirmed complete response, 1 stable disease). Of nine patients with RET fusion-positive thyroid cancer, seven demonstrated an objective response by RECIST 1.1 (all partial responses) and one additional patient demonstrated evidence of tumor regression (-21%). The confirmed overall response rate was 78% (7/9) (95% CI: 40%-97%). Included in the analysis is one patient with non-measurable disease at baseline (stable disease). Response assessments were performed by the local clinical trial sites.
Anti-tumor activity was observed regardless of RET mutation, RET fusion partner, and prior multikinase inhibitor treatment. One patient, with RET fusion-positive thyroid cancer, had RECIST target lesions in the central nervous system (CNS) and exhibited an intracranial partial response by RECIST 1.1, pending confirmation.
Overall safety analysis
Of the 82 patients in the safety analysis, most treatment-emergent adverse events were Grade 1 in severity and judged by the investigator as not related to LOXO-292. The treatment-emergent adverse events observed in ≥10% of patients, regardless of relationship to LOXO-292, were diarrhea (15% Grade 1, 7% Grade 2, 1% Grade 3), fatigue (9% Grade 1, 13% Grade 2, 0% ≥Grade 3), dry mouth (21% Grade 1, 0% ≥Grade 2), constipation (17% Grade 1, 2% Grade 2, 0% ≥Grade 3), hypomagnesemia (12% Grade 1, 1% Grade 2, 0% ≥Grade 3), cough (11% Grade 1, 1% Grade 2, 0% ≥Grade 3), headache (10% Grade 1, 1% Grade 2, 1% Grade 3) and nausea (9% Grade 1, 4% Grade 2, 0% ≥Grade 3). Four patients experienced adverse events ≥Grade 3 that were attributed to LOXO-292 (all Grade 3): tumor lysis syndrome, increased ALT/AST, diarrhea, and thrombocytopenia. All resolved with dose interruption. 160mg BID has been advanced as the Phase 2 dose, with dose exploration at 200mg BID ongoing to further characterize LOXO-292 safety and efficacy.
Interim clinical data were first presented at the 2018 ASCO Annual Meeting. Read the presentation from ASCO here.
Preclinical and clinical proof-of-concept data were also published in Annals of Oncology. That manuscript can be found here.
Preclinical data on the Loxo Oncology RET program were previously presented at the 2015 and 2016 AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics meetings. Those posters can be found here.
