Ivosidenib - CAS 1448347-49-6
Catalog number: B0084-474585
Category: Inhibitor
Not Intended for Therapeutic Use. For research use only.
Molecular Formula:
Molecular Weight:
Isocitrate Dehydrogenase (IDH)
Ivosidenib is an oral inhibitor that specifically inhibits a mutated form of IDH1 in the cytoplasm, which blocks the proliferation of tumor cells expressing IDH1.
Ordering Information
Catalog Number Size Price Stock Quantity
B0084-474585 100 mg $198 In stock
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Related CAS:
1448346-63-1 (racemic form)
Solid Powder
AG-120; AG120; (2S)-N-[(1S)-1-(2-chlorophenyl)-2-[(3,3-difluorocyclobutyl)amino]-2-oxoethyl]-1-(4-cyanopyridin-2-yl)-N-(5-fluoropyridin-3-yl)-5-oxopyrrolidine-2-carboxamide
Soluble in DMSO.
Store in a cool and dry place and at 0 - 4℃ for short term (days to weeks) or -65℃ for long term (months to years).
Shelf Life:
2 years
Boiling Point:
854.3±65.0 °C at 760 mmHg
1.51±0.1 g/cm3
Canonical SMILES:
1.Targeting isocitrate dehydrogenase (IDH) in cancer.
Fujii T;Khawaja MR;DiNardo CD;Atkins JT;Janku F Discov Med. 2016 May;21(117):373-80.
Isocitrate dehydrogenase (IDH) is an essential enzyme for cellular respiration in the tricarboxylic acid (TCA) cycle. Recurrent mutations in IDH1 or IDH2 are prevalent in several cancers including glioma, acute myeloid leukemia (AML), cholangiocarcinoma and chondrosarcoma. The mutated IDH1 and IDH2 proteins have a gain-of-function, neomorphic activity, catalyzing the reduction of α-ketoglutarate (α-KG) to 2-hydroxyglutarate (2-HG) by NADPH. Cancer-associated IDH mutations block normal cellular differentiation and promote tumorigenesis via the abnormal production of the oncometabolite 2-HG. High levels of 2-HG have been shown to inhibit α-KG dependent dioxygenases, including histone and deoxyribonucleic acid (DNA) demethylases, which play a key role in regulating the epigenetic state of cells. Current targeted inhibitors of IDH1 (AG120, IDH305), IDH2 (AG221), and pan-IDH1/2 (AG881) selectively inhibit mutant IDH protein and induce cell differentiation in in vitro and in vivo models. Preliminary results from phase I clinical trials with IDH inhibitors in patients with advanced hematologic malignancies have demonstrated an objective response rate ranging from 31% to 40% with durable responses (>1 year) observed.
2.Acquired resistance to IDH inhibition through trans or cis dimer-interface mutations.
Intlekofer AM;Shih AH;Wang B;Nazir A;Rustenburg AS;Albanese SK;Patel M;Famulare C;Correa FM;Takemoto N;Durani V;Liu H;Taylor J;Farnoud N;Papaemmanuil E;Cross JR;Tallman MS;Arcila ME;Roshal M;Petsko GA;Wu B;Choe S;Konteatis ZD;Biller SA;Chodera JD;Thompson CB;Levine RL;Stein EM Nature. 2018 Jul;559(7712):125-129. doi: 10.1038/s41586-018-0251-7. Epub 2018 Jun 27.
Somatic mutations in the isocitrate dehydrogenase 2 gene (IDH2) contribute to the pathogenesis of acute myeloid leukaemia (AML) through the production of the oncometabolite 2-hydroxyglutarate (2HG);1-8;. Enasidenib (AG-221) is an allosteric inhibitor that binds to the IDH2 dimer interface and blocks the production of 2HG by IDH2 mutants;9,10;. In a phase I/II clinical trial, enasidenib inhibited the production of 2HG and induced clinical responses in relapsed or refractory IDH2-mutant AML;11;. Here we describe two patients with IDH2-mutant AML who had a clinical response to enasidenib followed by clinical resistance, disease progression, and a recurrent increase in circulating levels of 2HG. We show that therapeutic resistance is associated with the emergence of second-site IDH2 mutations in trans, such that the resistance mutations occurred in the IDH2 allele without the neomorphic R140Q mutation. The in trans mutations occurred at glutamine 316 (Q316E) and isoleucine 319 (I319M), which are at the interface where enasidenib binds to the IDH2 dimer. The expression of either of these mutant disease alleles alone did not induce the production of 2HG; however, the expression of the Q316E or I319M mutation together with the R140Q mutation in trans allowed 2HG production that was resistant to inhibition by enasidenib.
3.Therapeutic choices after hypomethylating agent resistance for myelodysplastic syndromes.
Montalban-Bravo G;Garcia-Manero G;Jabbour E Curr Opin Hematol. 2018 Mar;25(2):146-153. doi: 10.1097/MOH.0000000000000400.
PURPOSE OF REVIEW: ;Hypomethylating agents (HMAs) are the standard of care for patients with myelodysplastic syndromes (MDS). Although these agents induce responses in up to 40% of patients, most patients ultimately experience loss of response. The purpose of this review is to provide an overview of the different therapies under development for MDS after HMA therapy.;RECENT FINDINGS: ;Recent advances in the understanding of MDS pathogenesis have led to the development of new potential therapies after HMA failure. Newer HMAs, less susceptible to in-vivo deamination, such as guadecitabine or ASTX727 have shown activity. Alterations of immune checkpoints in MDS have led to multiple clinical trials evaluating the activity of monoclonal antibodies targeting these proteins (pembrolizumab, nivolumab, ipilimumab). Different combinations and new formulations of cytotoxic agents, such as clofarabine or CPX-351, are newer options for specific subsets of patients. Finally, targeted agents inhibiting multiple kinases (rigosertib), BCL2 (venetoclax) or mutant IDH1 (ivosidenib), IDH2 (enasidenib), FLT3 (sorafenib, midostaurin) or spliceosome components (H3B-8800) are other novel options.;SUMMARY: ;Despite the poor prognosis associated with HMA failure, clinical trials, new cytotoxic agents and allogeneic stem-cell transplantation, can offer therapeutic opportunities for these patients for whom there is no standard of care.
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CAS 1448347-49-6 Ivosidenib

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