V158411 | CAS# 1174664-88-0 | selective Chk1 inhibitor

MedKoo Cat#: 563769 | Name: V158411

Description:

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

V158411 is a novel potent and selective Chk1 inhibitor. Inhibition of Chk1 with the small molecule inhibitor V158411 induces DNA damage and cell death in an unperturbed S-phase. V158411 abrogated gemcitabine and camptothecin induced cell cycle checkpoints, resulting in the expected modulation of cell cycle proteins and increased cell death in cancer cells. V158411 potentiated the cytotoxicity of gemcitabine, cisplatin, SN38 and camptothecin in a variety of p53 deficient human tumor cell lines in vitro, p53 proficient cells were unaffected. In nude mice, V158411 showed minimal toxicity as a single agent and in combination with irinotecan. In tumor bearing animals, V158411 was detected at high levels in the tumor with a long elimination half-life; no pharmacologically significant in vivo drug-drug interactions with irinotecan were identified through analysis of the pharmacokinetic profiles. V158411 potentiated the anti-tumor activity of irinotecan in a variety of human colon tumor xenograft models without additional systemic toxicity.

Chemical Structure

V158411

CAS#1174664-88-0

Theoretical Analysis

MedKoo Cat#: 563769

Name: V158411

CAS#: 1174664-88-0

Chemical Formula: C31H34N6O3

Exact Mass: 538.2692

Molecular Weight: 538.65

Elemental Analysis: C, 69.12; H, 6.36; N, 15.60; O, 8.91

Price and Availability

This product is currently not in stock but may be available through custom synthesis. To ensure cost efficiency, the minimum order quantity is 1 gram. The estimated lead time is 2 to 4 months, with pricing dependent on the complexity of the synthesis (typically high for intricate chemistries). Quotes for quantities below 1 gram will not be provided. To request a quote, please click the button below. Note: If this product becomes available in stock in the future, pricing will be listed accordingly.

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Related CAS #

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Synonym

V158411; V 158411; V-158411; VER00158411; VER 00158411; VER-00158411

IUPAC/Chemical Name

1-Benzyl-N-(5-(5-(3-(dimethylamino)-2,2-dimethylpropoxy)-1H-indol-2-yl)-6-oxo-1,6-dihydropyridin-3-yl)-1H-pyrazole-4-carboxamide

InChi Key

REQMZUHAMVOEON-UHFFFAOYSA-N

InChi Code

InChI=1S/C31H34N6O3/c1-31(2,19-36(3)4)20-40-25-10-11-27-22(12-25)13-28(35-27)26-14-24(16-32-30(26)39)34-29(38)23-15-33-37(18-23)17-21-8-6-5-7-9-21/h5-16,18,35H,17,19-20H2,1-4H3,(H,32,39)(H,34,38)

SMILES Code

O=C(C1=CN(CC2=CC=CC=C2)N=C1)NC(C=C3C(N4)=CC5=C4C=CC(OCC(C)(C)CN(C)C)=C5)=CNC3=O

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).

HS Tariff Code

2934.99.9001

More Info

Instruction

View handling instruction

Preparing Stock Solutions

The following data is based on the product molecular weight 538.65 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

1: Massey AJ, Stokes S, Browne H, Foloppe N, Fiumana A, Scrace S, Fallowfield M, Bedford S, Webb P, Baker L, Christie M, Drysdale MJ, Wood M. Identification of novel, in vivo active Chk1 inhibitors utilizing structure guided drug design. Oncotarget. 2015 Nov 3;6(34):35797-812. doi: 10.18632/oncotarget.5929. PubMed PMID: 26437226; PubMed Central PMCID: PMC4742142. 2: Rawlinson R, Massey AJ. γH2AX and Chk1 phosphorylation as predictive pharmacodynamic biomarkers of Chk1 inhibitor-chemotherapy combination treatments. BMC Cancer. 2014 Jul 4;14:483. doi: 10.1186/1471-2407-14-483. PubMed PMID: 24996846; PubMed Central PMCID: PMC4094550. 3: Massey AJ, Stephens P, Rawlinson R, McGurk L, Plummer R, Curtin NJ. mTORC1 and DNA-PKcs as novel molecular determinants of sensitivity to Chk1 inhibition. Mol Oncol. 2016 Jan;10(1):101-12. doi: 10.1016/j.molonc.2015.08.004. Epub 2015 Aug 25. PubMed PMID: 26471831; PubMed Central PMCID: PMC5528927. 4: Bryant C, Scriven K, Massey AJ. Inhibition of the checkpoint kinase Chk1 induces DNA damage and cell death in human Leukemia and Lymphoma cells. Mol Cancer. 2014 Jun 10;13:147. doi: 10.1186/1476-4598-13-147. PubMed PMID: 24913641; PubMed Central PMCID: PMC4082411. 5: Bryant C, Rawlinson R, Massey AJ. Chk1 inhibition as a novel therapeutic strategy for treating triple-negative breast and ovarian cancers. BMC Cancer. 2014 Aug 7;14:570. doi: 10.1186/1471-2407-14-570. PubMed PMID: 25104095; PubMed Central PMCID: PMC4137066. 6: Alsubhi N, Middleton F, Abdel-Fatah TM, Stephens P, Doherty R, Arora A, Moseley PM, Chan SY, Aleskandarany MA, Green AR, Rakha EA, Ellis IO, Martin SG, Curtin NJ, Madhusudan S. Chk1 phosphorylated at serine345 is a predictor of early local recurrence and radio-resistance in breast cancer. Mol Oncol. 2016 Feb;10(2):213-23. doi: 10.1016/j.molonc.2015.09.009. Epub 2015 Oct 3. PubMed PMID: 26459098; PubMed Central PMCID: PMC5528957. 7: Wayne J, Brooks T, Massey AJ. Inhibition of Chk1 with the small molecule inhibitor V158411 induces DNA damage and cell death in an unperturbed S-phase. Oncotarget. 2016 Dec 20;7(51):85033-85048. doi: 10.18632/oncotarget.13119. PubMed PMID: 27829224; PubMed Central PMCID: PMC5356717. 8: Massey AJ. Inhibition of ATR-dependent feedback activation of Chk1 sensitises cancer cells to Chk1 inhibitor monotherapy. Cancer Lett. 2016 Dec 1;383(1):41-52. doi: 10.1016/j.canlet.2016.09.024. Epub 2016 Sep 28. PubMed PMID: 27693461. 9: Geneste CC, Massey AJ. Cell Density Affects the Detection of Chk1 Target Engagement by the Selective Inhibitor V158411. SLAS Discov. 2018 Feb;23(2):144-153. doi: 10.1177/2472555217738534. Epub 2017 Oct 19. PubMed PMID: 29048945. 10: Massey AJ. A high content, high throughput cellular thermal stability assay for measuring drug-target engagement in living cells. PLoS One. 2018 Apr 4;13(4):e0195050. doi: 10.1371/journal.pone.0195050. eCollection 2018. PubMed PMID: 29617433; PubMed Central PMCID: PMC5884524.