SB-743921 | CAS#940929-33-9 | KSP inhibitor

MedKoo Cat#: 205790 | Name: SB-743921 HCl

Description:

WARNING: This product is for research use only, not for human or veterinary use.

SB-743921 is a synthetic small molecule with potential antineoplastic properties. SB-743921 selectively inhibits kinesin spindle protein (KSP), an important protein involved in the early stages of mitosis that is expressed in proliferating cells. Inhibition of KSP results in inhibition of mitotic spindle assembly and interrupts cell division, thereby causing cell cycle arrest and induction of apoptosis.

Chemical Structure

SB-743921 HCl

CAS#940929-33-9 (HCl)

Theoretical Analysis

MedKoo Cat#: 205790

Name: SB-743921 HCl

CAS#: 940929-33-9 (HCl)

Chemical Formula: C31H34Cl2N2O3

Exact Mass: 0.0000

Molecular Weight: 553.52

Elemental Analysis: C, 67.27; H, 6.19; Cl, 12.81; N, 5.06; O, 8.67

Price and Availability

Size	Price	Availability
5mg	USD 150.00	Ready to ship
10mg	USD 265.00	Ready to ship
25mg	USD 420.00	Ready to ship
50mg	USD 650.00	Ready to ship
100mg	USD 950.00	Ready to ship
200mg	USD 1,650.00	Ready to ship
500mg	USD 2,950.00	Ready to ship
1g	USD 5,250.00	Ready to ship

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Related CAS #

940929-33-9 (HCl) 618430-39-0 (free base)

Synonym

SB743921; SB 743921; SB743921; SB-743921 HCl; SB-743921 hydrochloride.

IUPAC/Chemical Name

(S)-N-(3-aminopropyl)-N-(1-(3-benzyl-7-chloro-4-oxo-4H-chromen-2-yl)-2-methylpropyl)-4-methylbenzamide hydrochloride

InChi Key

MLMZVWABFOLFGV-JCOPYZAKSA-N

InChi Code

InChI=1S/C31H33ClN2O3.ClH/c1-20(2)28(34(17-7-16-33)31(36)23-12-10-21(3)11-13-23)30-26(18-22-8-5-4-6-9-22)29(35)25-15-14-24(32)19-27(25)37-30;/h4-6,8-15,19-20,28H,7,16-18,33H2,1-3H3;1H/t28-;/m0./s1

SMILES Code

O=C(N(CCCN)[C@H](C1=C(CC2=CC=CC=C2)C(C3=C(O1)C=C(Cl)C=C3)=O)C(C)C)C4=CC=C(C)C=C4.[H]Cl

Appearance

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).

HS Tariff Code

2934.99.9001

More Info

SB-743921, Cytokinetics's second KSP inhibitor to enter clinical trials, is structurally distinct from ispinesib, Cytokinetics' most advanced anti-cancer drug candidate. SB-743921 was the subject of a Phase I/II clinical trial in Hodgkin and non-Hodgkin Lymphoma that has been completed

Product Data

Product Data

Certificate of Analysis

View CoA: current batch, Lot#C8R12B06

View CoA: previous batch, Lot#BCP30315

QC Data

View QC data: current batch, Lot# C8R12B06

View QC data: previous batch, Lot#BCP30315

Safety Data Sheet (SDS)

View Safety Data Sheet (SDS)

Instruction

View handling instruction

Biological target:

SB-743921 HCl is an inhibitor of the mitotic kinesin KSP (Eg5) with a Ki of 0.1 nM.

In vitro activity:

SB-743921 showed promising antitumor activity in breast cancer cell lines by reducing proliferation, inducing cell-cycle arrest, and promoting apoptosis. SB-743921 reduced colony formation ability and altered the expression of key proteins associated with cell arrest and apoptosis, suggesting its potential in breast cancer treatment. Reference: Anticancer Drugs. 2016 Oct;27(9):863-72. https://pubmed.ncbi.nlm.nih.gov/27379929/

In vivo activity:

In Ewing sarcoma xenograft mouse models, the treatment combination of SB-743921 and VIC-1911 led to a significant reduction in tumor size and showed superior overall survival compared to vehicle or monotherapy arms. Reference: Cancers (Basel). 2023 Oct 10;15(20):4911. https://pubmed.ncbi.nlm.nih.gov/37894278/

	Solvent	mg/mL	mM	comments
Solubility
	Water	10.0	18.07

Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 553.52 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.

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. Zhu L, Xiao F, Yu Y, Wang H, Fang M, Yang Y, Sun H, Wang L, Sheng Y. KSP inhibitor SB743921 inhibits growth and induces apoptosis of breast cancer cells by regulating p53, Bcl-2, and DTL. Anticancer Drugs. 2016 Oct;27(9):863-72. doi: 10.1097/CAD.0000000000000402. PMID: 27379929; PMCID: PMC5010280. 2. Song IS, Jeong YJ, Nyamaa B, Jeong SH, Kim HK, Kim N, Ko KS, Rhee BD, Han J. KSP inhibitor SB743921 induces death of multiple myeloma cells via inhibition of the NF-κB signaling pathway. BMB Rep. 2015 Oct;48(10):571-6. doi: 10.5483/bmbrep.2015.48.10.015. PMID: 25772758; PMCID: PMC4911184. 3. Turaga SM, Vishwakarma V, Hembruff SL, Gibbs BK, Sabu P, Puri RV, Pathak HB, Samuel G, Godwin AK. Inducing Mitotic Catastrophe as a Therapeutic Approach to Improve Outcomes in Ewing Sarcoma. Cancers (Basel). 2023 Oct 10;15(20):4911. doi: 10.3390/cancers15204911. PMID: 37894278; PMCID: PMC10605681. 4. Shi Y, Cui X, Jiang T, Pan Y, Lin Y, Feng X, Ding Z, Yang C, Tan Y, Wang H, Dong L. The therapeutic effect of KSP inhibitors in preclinical models of cholangiocarcinoma. Cell Death Dis. 2022 Sep 19;13(9):799. doi: 10.1038/s41419-022-05247-0. PMID: 36123339; PMCID: PMC9485230.

In vitro protocol:

In vivo protocol:

1. Turaga SM, Vishwakarma V, Hembruff SL, Gibbs BK, Sabu P, Puri RV, Pathak HB, Samuel G, Godwin AK. Inducing Mitotic Catastrophe as a Therapeutic Approach to Improve Outcomes in Ewing Sarcoma. Cancers (Basel). 2023 Oct 10;15(20):4911. doi: 10.3390/cancers15204911. PMID: 37894278; PMCID: PMC10605681. 2. Shi Y, Cui X, Jiang T, Pan Y, Lin Y, Feng X, Ding Z, Yang C, Tan Y, Wang H, Dong L. The therapeutic effect of KSP inhibitors in preclinical models of cholangiocarcinoma. Cell Death Dis. 2022 Sep 19;13(9):799. doi: 10.1038/s41419-022-05247-0. PMID: 36123339; PMCID: PMC9485230.

1: Viswanath AN, Pae AN. Resistance by allostery: a novel perspective for eg5-targeted drug design. J Med Chem. 2013 Aug 22;56(16):6314-6. doi: 10.1021/jm401071u. Epub 2013 Jul 30. PubMed PMID: 23899248. 2: Talapatra SK, Anthony NG, Mackay SP, Kozielski F. Mitotic kinesin Eg5 overcomes inhibition to the phase I/II clinical candidate SB743921 by an allosteric resistance mechanism. J Med Chem. 2013 Aug 22;56(16):6317-29. doi: 10.1021/jm4006274. PubMed PMID: 23875972. 3: Good JA, Wang F, Rath O, Kaan HY, Talapatra SK, PodgÃ³rski D, MacKay SP, Kozielski F. Optimized S-trityl-L-cysteine-based inhibitors of kinesin spindle protein with potent in vivo antitumor activity in lung cancer xenograft models. J Med Chem. 2013 Mar 14;56(5):1878-93. doi: 10.1021/jm3014597. Epub 2013 Feb 27. PubMed PMID: 23394180; PubMed Central PMCID: PMC3759169. 4: Holen KD, Belani CP, Wilding G, Ramalingam S, Volkman JL, Ramanathan RK, Vasist LS, Bowen CJ, Hodge JP, Dar MM, Ho PT. A first in human study of SB-743921, a kinesin spindle protein inhibitor, to determine pharmacokinetics, biologic effects and establish a recommended phase II dose. Cancer Chemother Pharmacol. 2011 Feb;67(2):447-54. doi: 10.1007/s00280-010-1346-5. Epub 2010 May 12. PubMed PMID: 20461380. 5: Tomillero A, Moral MA. Gateways to clinical trials. Methods Find Exp Clin Pharmacol. 2009 Jan-Feb;31(1):47-57. PubMed PMID: 19357798. 6: BayÃ©s M, Rabasseda X, Prous JR. Gateways to clinical trials. Methods Find Exp Clin Pharmacol. 2006 Oct;28(8):533-91. PubMed PMID: 17136234.