Ivosidenib
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Hodoodo CAT#: H206507

CAS#: 1448347-49-6 (Ivosidenib)

Description: Ivosidenib, also known as AG-120 and RG-120, is an orally available inhibitor of isocitrate dehydrogenase type 1 (IDH1), with potential antineoplastic activity. Ivosidenib specifically inhibits a mutated form of IDH1 in the cytoplasm, which inhibits the formation of the oncometabolite, 2-hydroxyglutarate (2HG). This may lead to both an induction of cellular differentiation and an inhibition of cellular proliferation in IDH1-expressing tumor cells.


Chemical Structure

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Ivosidenib
CAS# 1448347-49-6 (Ivosidenib)

Theoretical Analysis

Hodoodo Cat#: H206507
Name: Ivosidenib
CAS#: 1448347-49-6 (Ivosidenib)
Chemical Formula: C28H22ClF3N6O3
Exact Mass: 582.14
Molecular Weight: 582.970
Elemental Analysis: C, 57.69; H, 3.80; Cl, 6.08; F, 9.78; N, 14.42; O, 8.23

Price and Availability

Size Price Availability Quantity
10mg USD 90 Ready to ship
25mg USD 150 Ready to ship
50mg USD 250 Ready to ship
100mg USD 450 Ready to ship
200mg USD 750 Ready to ship
500mg USD 1650 Ready to ship
1g USD 2950 Ready to ship
2g USD 5250 Ready to ship
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Related CAS #: 1448347-49-6 (Ivosidenib)   1448346-63-1 (AG-120 racemic),  

Synonym: Ivosidenib, AG-120; AG120; AG 120; RG-120; RG 120; RG120; Tibsovo;

IUPAC/Chemical Name: (S)-N-((S)-1-(2-chlorophenyl)-2-((3,3-difluorocyclobutyl)amino)-2-oxoethyl)-1-(4-cyanopyridin-2-yl)-N-(5-fluoropyridin-3-yl)-5-oxopyrrolidine-2-carboxamide

InChi Key: WIJZXSAJMHAVGX-DHLKQENFSA-N

InChi Code: InChI=1S/C28H22ClF3N6O3/c29-21-4-2-1-3-20(21)25(26(40)36-18-11-28(31,32)12-18)37(19-10-17(30)14-34-15-19)27(41)22-5-6-24(39)38(22)23-9-16(13-33)7-8-35-23/h1-4,7-10,14-15,18,22,25H,5-6,11-12H2,(H,36,40)/t22-,25-/m0/s1

SMILES Code: O=C([C@H](CC1)N(C2=NC=CC(C#N)=C2)C1=O)N([C@@H](C3=CC=CC=C3Cl)C(NC4CC(F)(F)C4)=O)C5=CC(F)=CN=C5

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, 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).

HS Tariff Code: 2934.99.9001

More Info: AC120 and Ivosidenib have the same molecule formula and molecule weight. Ivosidenib has CAS#1448347-49-6, is a S,S-isomer. AC120 has CAS#1448346-63-1, is a racemic.

Biological target: Ivosidenib (AG-120) is an inhibitor of isocitrate dehydrogenase 1 mutant (mIDH1) enzyme.
In vitro activity: A549 and SK-MES-1 cell viabilities were lower after treatment with ivosidenib for 24, 48, and 72 h. The suppression rates were dose-dependent but not time-dependent (Figure 1C). As shown in (Figure 1D), the number of colonies inversely correlated with concentrations of ivosidenib. This study performed a Transwell array in A549 and SK-MES-1 cells to evaluate the effect of ivosidenib on cell invasion and migration and found that the invasion and migration abilities of A549 and SK-MES-1 cells were significantly lower in the ivosidenib-treatment group than in the control group (Figures 3A, B). Reference: Front Oncol. 2021; 11: 626605. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8042334/
In vivo activity: AG-120 showed robust tumor 2-HG reduction in female nude BALB/c mice inoculated with HT1080 cells. Each mouse received a single oral dose of vehicle or AG-120 at 50 or 150 mg/kg by gavage. Tumor 2-HG concentration declined rapidly, with maximum inhibition (92.0% and 95.2% at the 50 mg/kg and 150 mg/kg doses, respectively) achieved at ∼12 h post dose. Tumor 2-HG concentrations approached baseline levels 48–72 h following a single dose of AG-120 (Figure 1), consistent with the reversible nature of AG-120 inhibition. Reference: ACS Med Chem Lett. 2018 Apr 12; 9(4): 300–305. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5900343/

Solubility Data

Solvent Max Conc. mg/mL Max Conc. mM
Solubility
DMSO 56.3 96.63
DMF 30.0 51.46
Ethanol 65.0 111.50

Preparing Stock Solutions

The following data is based on the product molecular weight 582.97 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Recalculate based on batch purity %
Concentration / Solvent Volume / Mass 1 mg 5 mg 10 mg
1 mM 1.15 mL 5.76 mL 11.51 mL
5 mM 0.23 mL 1.15 mL 2.3 mL
10 mM 0.12 mL 0.58 mL 1.15 mL
50 mM 0.02 mL 0.12 mL 0.23 mL
Formulation protocol: 1. Wu J, Chen R, Shen H, Yan T, Qian Y, Zhang Y, Huang Z, Kong P, Pang M, Zhang X. Transcriptome Analysis of Ivosidenib-Mediated Inhibitory Functions on Non-Small Cell Lung Cancer. Front Oncol. 2021 Mar 30;11:626605. doi: 10.3389/fonc.2021.626605. PMID: 33859940; PMCID: PMC8042334. 2. Popovici-Muller J, Lemieux RM, Artin E, Saunders JO, Salituro FG, Travins J, Cianchetta G, Cai Z, Zhou D, Cui D, Chen P, Straley K, Tobin E, Wang F, David MD, Penard-Lacronique V, Quivoron C, Saada V, de Botton S, Gross S, Dang L, Yang H, Utley L, Chen Y, Kim H, Jin S, Gu Z, Yao G, Luo Z, Lv X, Fang C, Yan L, Olaharski A, Silverman L, Biller S, Su SM, Yen K. Discovery of AG-120 (Ivosidenib): A First-in-Class Mutant IDH1 Inhibitor for the Treatment of IDH1 Mutant Cancers. ACS Med Chem Lett. 2018 Jan 19;9(4):300-305. doi: 10.1021/acsmedchemlett.7b00421. PMID: 29670690; PMCID: PMC5900343.
In vitro protocol: 1. Wu J, Chen R, Shen H, Yan T, Qian Y, Zhang Y, Huang Z, Kong P, Pang M, Zhang X. Transcriptome Analysis of Ivosidenib-Mediated Inhibitory Functions on Non-Small Cell Lung Cancer. Front Oncol. 2021 Mar 30;11:626605. doi: 10.3389/fonc.2021.626605. PMID: 33859940; PMCID: PMC8042334. 2. Popovici-Muller J, Lemieux RM, Artin E, Saunders JO, Salituro FG, Travins J, Cianchetta G, Cai Z, Zhou D, Cui D, Chen P, Straley K, Tobin E, Wang F, David MD, Penard-Lacronique V, Quivoron C, Saada V, de Botton S, Gross S, Dang L, Yang H, Utley L, Chen Y, Kim H, Jin S, Gu Z, Yao G, Luo Z, Lv X, Fang C, Yan L, Olaharski A, Silverman L, Biller S, Su SM, Yen K. Discovery of AG-120 (Ivosidenib): A First-in-Class Mutant IDH1 Inhibitor for the Treatment of IDH1 Mutant Cancers. ACS Med Chem Lett. 2018 Jan 19;9(4):300-305. doi: 10.1021/acsmedchemlett.7b00421. PMID: 29670690; PMCID: PMC5900343.
In vivo protocol: 1. Wu J, Chen R, Shen H, Yan T, Qian Y, Zhang Y, Huang Z, Kong P, Pang M, Zhang X. Transcriptome Analysis of Ivosidenib-Mediated Inhibitory Functions on Non-Small Cell Lung Cancer. Front Oncol. 2021 Mar 30;11:626605. doi: 10.3389/fonc.2021.626605. PMID: 33859940; PMCID: PMC8042334. 2. Popovici-Muller J, Lemieux RM, Artin E, Saunders JO, Salituro FG, Travins J, Cianchetta G, Cai Z, Zhou D, Cui D, Chen P, Straley K, Tobin E, Wang F, David MD, Penard-Lacronique V, Quivoron C, Saada V, de Botton S, Gross S, Dang L, Yang H, Utley L, Chen Y, Kim H, Jin S, Gu Z, Yao G, Luo Z, Lv X, Fang C, Yan L, Olaharski A, Silverman L, Biller S, Su SM, Yen K. Discovery of AG-120 (Ivosidenib): A First-in-Class Mutant IDH1 Inhibitor for the Treatment of IDH1 Mutant Cancers. ACS Med Chem Lett. 2018 Jan 19;9(4):300-305. doi: 10.1021/acsmedchemlett.7b00421. PMID: 29670690; PMCID: PMC5900343.

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2: Hernandez Burgos P, Patel J, Chen A. Ivosidenib induction therapy complicated by myopericarditis and cardiogenic shock: A case report and literature review. J Oncol Pharm Pract. 2019 Aug 5:1078155219865934. doi: 10.1177/1078155219865934. [Epub ahead of print] PubMed PMID: 31382862.

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5: Fan B, Mellinghoff IK, Wen PY, Lowery MA, Goyal L, Tap WD, Pandya SS, Manyak E, Jiang L, Liu G, Nimkar T, Gliser C, Prahl Judge M, Agresta S, Yang H, Dai D. Clinical pharmacokinetics and pharmacodynamics of ivosidenib, an oral, targeted inhibitor of mutant IDH1, in patients with advanced solid tumors. Invest New Drugs. 2019 Apr 26. doi: 10.1007/s10637-019-00771-x. [Epub ahead of print] PubMed PMID: 31028664.

6: Dai D, Yang H, Nabhan S, Liu H, Hickman D, Liu G, Zacher J, Vutikullird A, Prakash C, Agresta S, Bowden C, Fan B. Effect of itraconazole, food, and ethnic origin on the pharmacokinetics of ivosidenib in healthy subjects. Eur J Clin Pharmacol. 2019 Aug;75(8):1099-1108. doi: 10.1007/s00228-019-02673-6. Epub 2019 Apr 23. PubMed PMID: 31011758.

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10: Nassereddine S, Lap CJ, Tabbara IA. Evaluating ivosidenib for the treatment of relapsed/refractory AML: design, development, and place in therapy. Onco Targets Ther. 2018 Dec 28;12:303-308. doi: 10.2147/OTT.S182443. eCollection 2019. Review. PubMed PMID: 30643428; PubMed Central PMCID: PMC6314316.

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19: Sidaway P. Ivosidenib effective in IDH1-mutant AML. Nat Rev Clin Oncol. 2018 Aug;15(8):472. doi: 10.1038/s41571-018-0057-4. PubMed PMID: 29925981.

20: DiNardo CD, Stein EM, de Botton S, Roboz GJ, Altman JK, Mims AS, Swords R, Collins RH, Mannis GN, Pollyea DA, Donnellan W, Fathi AT, Pigneux A, Erba HP, Prince GT, Stein AS, Uy GL, Foran JM, Traer E, Stuart RK, Arellano ML, Slack JL, Sekeres MA, Willekens C, Choe S, Wang H, Zhang V, Yen KE, Kapsalis SM, Yang H, Dai D, Fan B, Goldwasser M, Liu H, Agresta S, Wu B, Attar EC, Tallman MS, Stone RM, Kantarjian HM. Durable Remissions with Ivosidenib in IDH1-Mutated Relapsed or Refractory AML. N Engl J Med. 2018 Jun 21;378(25):2386-2398. doi: 10.1056/NEJMoa1716984. Epub 2018 Jun 2. PubMed PMID: 29860938.