BMS-536924
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MedKoo CAT#: 200521

CAS#: 468740-43-4

Description: BMS-536924 is a potent small molecule inhibitor of IGF-IR, which shows antitumor activity in multiple tumor models, including sarcoma.


Chemical Structure

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BMS-536924
CAS# 468740-43-4

Theoretical Analysis

MedKoo Cat#: 200521
Name: BMS-536924
CAS#: 468740-43-4
Chemical Formula: C25H26ClN5O3
Exact Mass: 479.17242
Molecular Weight: 479.96
Elemental Analysis: C, 62.56; H, 5.46; Cl, 7.39; N, 14.59; O, 10.00

Price and Availability

Size Price Availability Quantity
25.0mg USD 250.0 2 Weeks
50.0mg USD 450.0 2 Weeks
100.0mg USD 750.0 2 Weeks
200.0mg USD 1250.0 2 Weeks
500.0mg USD 1950.0 2 Weeks
1.0g USD 2950.0 2 Weeks
2.0g USD 5250.0 2 Weeks
Bulk inquiry

Synonym: BMS536924; BMS-536924; BMS 536924.

IUPAC/Chemical Name: (S)-4-((2-(3-chlorophenyl)-2-hydroxyethyl)amino)-3-(4-methyl-6-morpholino-1H-benzo[d]imidazol-2-yl)pyridin-2(1H)-one

InChi Key: ZWVZORIKUNOTCS-OAQYLSRUSA-N

InChi Code: InChI=1S/C25H26ClN5O3/c1-15-11-18(31-7-9-34-10-8-31)13-20-23(15)30-24(29-20)22-19(5-6-27-25(22)33)28-14-21(32)16-3-2-4-17(26)12-16/h2-6,11-13,21,32H,7-10,14H2,1H3,(H,29,30)(H2,27,28,33)/t21-/m1/s1

SMILES Code: O=C1C(C2=NC3=C(C)C=C(N4CCOCC4)C=C3N2)=C(NC[C@H](C5=CC=CC(Cl)=C5)O)C=CN1

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: >5 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

Product Data:

Biological target: BMS-536924 is an orally active, competitive and selective insulin-like growth factor receptor (IGF-1R) kinase and insulin receptor (IR) inhibitor with IC50s of 100 nM and 73 nM, respectively.
In vitro activity: Treatment of mouse MLL-AF9 acute myelogenous leukemia cells with BMS-536924, an IGF1R/insulin receptor-selective tyrosine kinase inhibitor, blocked cell growth, suggesting its efficacy in this model may be due to inhibition of insulin receptor and/or related tyrosine kinases, and raising the possibility that similar IGF1R inhibitors in clinical development may be acting through alternate/related pathways. Reference: Exp Hematol. 2012 Sep;40(9):715-723.e6. https://pubmed.ncbi.nlm.nih.gov/22613471/
In vivo activity: The results show that the low dose of BMS-536924 (20 mg/kg) led to an intermediate level of tumor growth suppression, whereas the high dose of BMS-536924 (40 mg/kg) led to a significant inhibition on M059K-R and M059K tumor growth (Figure 5A and B) (P<0.05). Consistent with the in vitro apoptosis data showed above, BMS-536924 induced dramatic apoptotic characteristics in tumors as examined using TUNEL, DAPI, and hematoxylin and eosin (H&E) staining assays (Figure 5C). At the same time, administration of BMS-536924 was well-tolerated by healthy mice, without significant signs of overt toxicity on the main mice organs, including lung, liver, and kidney, or loss of weight (P<0.05) (Figure 5D). Reference: Onco Targets Ther. 2015; 8: 689–697. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4396459/

Solubility Data

Solvent Max Conc. mg/mL Max Conc. mM
Solubility
DMSO 51.0 106.26
DMF 12.0 25.0
DMF:PBS (pH 7.2) (1:9) 0.1 0.21

Preparing Stock Solutions

The following data is based on the product molecular weight 479.96 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. Adachi Y, Ohashi H, Imsumran A, Yamamoto H, Matsunaga Y, Taniguchi H, Nosho K, Suzuki H, Sasaki Y, Arimura Y, Carbone DP, Imai K, Shinomura Y. The effect of IGF-I receptor blockade for human esophageal squamous cell carcinoma and adenocarcinoma. Tumour Biol. 2014 Feb;35(2):973-85. doi: 10.1007/s13277-013-1131-2. Epub 2013 Sep 13. PMID: 24026884. 2. Jenkins CR, Shevchuk OO, Giambra V, Lam SH, Carboni JM, Gottardis MM, Holzenberger M, Pollak M, Humphries RK, Weng AP. IGF signaling contributes to malignant transformation of hematopoietic progenitors by the MLL-AF9 oncoprotein. Exp Hematol. 2012 Sep;40(9):715-723.e6. doi: 10.1016/j.exphem.2012.05.003. Epub 2012 May 18. PMID: 22613471. 3. Zhou Q. BMS-536924, an ATP-competitive IGF-1R/IR inhibitor, decreases viability and migration of temozolomide-resistant glioma cells in vitro and suppresses tumor growth in vivo. Onco Targets Ther. 2015 Apr 2;8:689-97. doi: 10.2147/OTT.S80047. PMID: 25897243; PMCID: PMC4396459.
In vitro protocol: 1. Adachi Y, Ohashi H, Imsumran A, Yamamoto H, Matsunaga Y, Taniguchi H, Nosho K, Suzuki H, Sasaki Y, Arimura Y, Carbone DP, Imai K, Shinomura Y. The effect of IGF-I receptor blockade for human esophageal squamous cell carcinoma and adenocarcinoma. Tumour Biol. 2014 Feb;35(2):973-85. doi: 10.1007/s13277-013-1131-2. Epub 2013 Sep 13. PMID: 24026884. 2. Jenkins CR, Shevchuk OO, Giambra V, Lam SH, Carboni JM, Gottardis MM, Holzenberger M, Pollak M, Humphries RK, Weng AP. IGF signaling contributes to malignant transformation of hematopoietic progenitors by the MLL-AF9 oncoprotein. Exp Hematol. 2012 Sep;40(9):715-723.e6. doi: 10.1016/j.exphem.2012.05.003. Epub 2012 May 18. PMID: 22613471.
In vivo protocol: 1. Zhou Q. BMS-536924, an ATP-competitive IGF-1R/IR inhibitor, decreases viability and migration of temozolomide-resistant glioma cells in vitro and suppresses tumor growth in vivo. Onco Targets Ther. 2015 Apr 2;8:689-97. doi: 10.2147/OTT.S80047. PMID: 25897243; PMCID: PMC4396459.

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1: Velaparthi U, Saulnier MG, Wittman MD, Liu P, Frennesson DB, Zimmermann K, Carboni JM, Gottardis M, Li A, Greer A, Clarke W, Yang Z, Menard K, Lee FY, Trainor G, Vyas D. Insulin-like growth factor-1 receptor (IGF-1R) kinase inhibitors: SAR of a series of 3-[6-(4-substituted-piperazin-1-yl)-4-methyl-1H-benzimidazol-2-yl]-1H-pyridine-2- one. Bioorg Med Chem Lett. 2010 May 15;20(10):3182-5. Epub 2010 Mar 27. PubMed PMID: 20399649.

2: Novosyadlyy R, Lann DE, Vijayakumar A, Rowzee A, Lazzarino DA, Fierz Y, Carboni JM, Gottardis MM, Pennisi PA, Molinolo AA, Kurshan N, Mejia W, Santopietro S, Yakar S, Wood TL, LeRoith D. Insulin-mediated acceleration of breast cancer development and progression in a nonobese model of type 2 diabetes. Cancer Res. 2010 Jan 15;70(2):741-51. Epub 2010 Jan 12. PubMed PMID: 20068149.

3: Wahner Hendrickson AE, Haluska P, Schneider PA, Loegering DA, Peterson KL, Attar R, Smith BD, Erlichman C, Gottardis M, Karp JE, Carboni JM, Kaufmann SH. Expression of insulin receptor isoform A and insulin-like growth factor-1 receptor in human acute myelogenous leukemia: effect of the dual-receptor inhibitor BMS-536924 in vitro. Cancer Res. 2009 Oct 1;69(19):7635-43. Epub 2009 Sep 29. PubMed PMID: 19789352; PubMed Central PMCID: PMC2762752.

4: Beauchamp MC, Knafo A, Yasmeen A, Carboni JM, Gottardis MM, Pollak MN, Gotlieb WH. BMS-536924 sensitizes human epithelial ovarian cancer cells to the PARP inhibitor, 3-aminobenzamide. Gynecol Oncol. 2009 Nov;115(2):193-8. Epub 2009 Aug 21. PubMed PMID: 19699512.

5: Avnet S, Sciacca L, Salerno M, Gancitano G, Cassarino MF, Longhi A, Zakikhani M, Carboni JM, Gottardis M, Giunti A, Pollak M, Vigneri R, Baldini N. Insulin receptor isoform A and insulin-like growth factor II as additional treatment targets in human osteosarcoma. Cancer Res. 2009 Mar 15;69(6):2443-52. Epub 2009 Mar 3. PubMed PMID: 19258511.

6: Xu Y, Wang GS, Sun W, Yang XH, Xu LB. [Progress in the studies on small molecule IGF-1R inhibitors]. Yao Xue Xue Bao. 2008 Oct;43(10):979-84. Review. Chinese. PubMed PMID: 19127859.

7: Litzenburger BC, Kim HJ, Kuiatse I, Carboni JM, Attar RM, Gottardis MM, Fairchild CR, Lee AV. BMS-536924 reverses IGF-IR-induced transformation of mammary epithelial cells and causes growth inhibition and polarization of MCF7 cells. Clin Cancer Res. 2009 Jan 1;15(1):226-37. PubMed PMID: 19118050; PubMed Central PMCID: PMC2819349.

8: Huang F, Greer A, Hurlburt W, Han X, Hafezi R, Wittenberg GM, Reeves K, Chen J, Robinson D, Li A, Lee FY, Gottardis MM, Clark E, Helman L, Attar RM, Dongre A, Carboni JM. The mechanisms of differential sensitivity to an insulin-like growth factor-1 receptor inhibitor (BMS-536924) and rationale for combining with EGFR/HER2 inhibitors. Cancer Res. 2009 Jan 1;69(1):161-70. PubMed PMID: 19117999.

9: Law JH, Habibi G, Hu K, Masoudi H, Wang MY, Stratford AL, Park E, Gee JM, Finlay P, Jones HE, Nicholson RI, Carboni J, Gottardis M, Pollak M, Dunn SE. Phosphorylated insulin-like growth factor-i/insulin receptor is present in all breast cancer subtypes and is related to poor survival. Cancer Res. 2008 Dec 15;68(24):10238-46. PubMed PMID: 19074892.

10: Haluska P, Carboni JM, TenEyck C, Attar RM, Hou X, Yu C, Sagar M, Wong TW, Gottardis MM, Erlichman C. HER receptor signaling confers resistance to the insulin-like growth factor-I receptor inhibitor, BMS-536924. Mol Cancer Ther. 2008 Sep;7(9):2589-98. Epub 2008 Sep 2. PubMed PMID: 18765823; PubMed Central PMCID: PMC2614316.

BMS-536924

10.0mg / Not available


Additional Information

BMS-535924 is a potent inhibitor of the IGF-1 receptor in vitro  (IC50 = 100 nM). BMS-536924 has been shown to inhibit the catalytic activity of IGF-1R and its down stream signaling components such as Akt and MAPK in cells; it also inhibits proliferation in a wide variety of human cancer cell lines including, colon, breast, lung, pancreas, prostate, sarcoma and multiple myeloma. In vivo, BMS-536924 inhibits tumor growth in an IGF-1R-dependent tumor model (IGF-1R Sal) as well as in a broad range of human tumor xenografts.