V158411

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

MedKoo CAT#: 563769

CAS#: 1174664-88-0

Description: 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

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V158411
CAS# 1174664-88-0
Instruction

Theoretical Analysis

MedKoo Cat#: 563769
Name: V158411
CAS#: 1174664-88-0
Chemical Formula: C31H34N6O3
Exact Mass: 538.27
Molecular Weight: 538.650
Elemental Analysis: C, 69.12; H, 6.36; N, 15.60; O, 8.91

Price and Availability

This product is not in stock, which may be available by custom synthesis. For cost-effective reason, minimum order is 1g (price is usually high, lead time is 2~3 months, depending on the technical challenge). Quote less than 1g will not be provided. To request quote, please email to sales @medkoo.com or click below button.
Note: Price will be listed if it is available in the future.

Request quote for custom synthesis

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:

Biological target:
In vitro activity:
In vivo activity:

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.

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:
In vitro protocol:
In vivo protocol:

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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.