MK-8776 | SCH900776 | CAS#891494-63-6 | 891494-64-7 | CHK inhibitor

MedKoo Cat#: 202573 | Name: SCH900776

Description:

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

SCH900776, also known as MK-8776. is an agent targeting cell cycle checkpoint kinase 1 (Chk1) with potential radiosensitization and chemosensitization activities. Chk1 inhibitor SCH900776 specifically binds to and inhibits Chk1, which may result in tumor cells bypassing Chk1-dependent cell cycle arrest in the S and G2/M phases to undergo DNA repair prior to entry into mitosis; tumor cells may thus be sensitized to the DNA-damaging effects of ionizing radiation and alkylating chemotherapeutic agents.

Chemical Structure

SCH900776

CAS#891494-63-6

Theoretical Analysis

MedKoo Cat#: 202573

Name: SCH900776

CAS#: 891494-63-6

Chemical Formula: C15H18BrN7

Exact Mass: 375.0807

Molecular Weight: 376.25

Elemental Analysis: C, 47.88; H, 4.82; Br, 21.24; N, 26.06

Price and Availability

Size	Price	Availability
5mg	USD 150.00	Ready to ship
10mg	USD 250.00	Ready to ship
25mg	USD 550.00	Ready to ship
50mg	USD 950.00	Ready to ship
100mg	USD 1,650.00	Ready to ship
200mg	USD 2,850.00	Ready to ship

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Related CAS #

891494-63-6 891494-64-7 (S-isomer)

Synonym

SCH900776; SCH-900776; SCH 900776; MK8776; MK-8776; MK 8776;

IUPAC/Chemical Name

(R)-6-bromo-3-(1-methyl-1H-pyrazol-4-yl)-5-(piperidin-3-yl)pyrazolo[1,5-a]pyrimidin-7-amine

InChi Key

GMIZZEXBPRLVIV-SECBINFHSA-N

InChi Code

InChI=1S/C15H18BrN7/c1-22-8-10(6-19-22)11-7-20-23-14(17)12(16)13(21-15(11)23)9-3-2-4-18-5-9/h6-9,18H,2-5,17H2,1H3/t9-/m1/s1

SMILES Code

NC1=C(Br)C([C@H]2CNCCC2)=NC3=C(C4=CN(C)N=C4)C=NN13

Appearance

white to off-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

Product Data

Product Data

Certificate of Analysis

View CoA: current batch, Lot#BBC61102

View CoA: current batch, Lot#T23D02P06

QC Data

View QC data: current batch, Lot#BBC61102

View QC data: current batch, Lot#T23D02P06

Safety Data Sheet (SDS)

View Safety Data Sheet (SDS)

Instruction

View handling instruction

Biological target:

SCH900776 is a potent, selective inhibitor of checkpoint kinase1 (Chk1) with an IC50 of 3 nM and shows 50- and 500-fold selectivity over CDK2 and Chk2, respectively.

In vitro activity:

SCH900776 has potential as a differentiation therapy for acute promyelocytic leukemia (APL). Treatment of APL cells with SCH900776 indicated differentiation, as evident by decreased PML-RARα levels, increased expression of CD11b, and increased granulocytic activity. SCH900776 caused significant modulation of pathways and upstream regulators involved in inflammatory response and cell cycle control. Reference: Biochem Pharmacol. 2023 Aug;214:115675. https://pubmed.ncbi.nlm.nih.gov/37406967/

In vivo activity:

In mice, administration of SCH900776 18 hours after gemcitabine elicited positivity for the DNA damage marker γH2AX; occurring at relatively low dose of gemcitabine. In both tumor cell cultures and xenografts, SCH900776 enhanced cell killing of cells reversibly arrested in S phase by gemcitabine. Reference: Oncotarget. 2017 Jun 28;8(40):67754-67768. https://pubmed.ncbi.nlm.nih.gov/28978069/

	Solvent	mg/mL	mM
Solubility
	DMF	5.0	13.30
	DMSO	20.0	53.20
	Ethanol	3.0	8.00
	PBS (pH 7.2)	10.0	26.60

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 376.25 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. Franza M, Albanesi J, Mancini B, Pennisi R, Leone S, Acconcia F, Bianchi F, di Masi A. The clinically relevant CHK1 inhibitor MK-8776 induces the degradation of the oncogenic protein PML-RARα and overcomes ATRA resistance in acute promyelocytic leukemia cells. Biochem Pharmacol. 2023 Aug;214:115675. doi: 10.1016/j.bcp.2023.115675. Epub 2023 Jul 3. PMID: 37406967. 2. Cui Q, Cai CY, Wang JQ, Zhang S, Gupta P, Ji N, Yang Y, Dong X, Yang DH, Chen ZS. Chk1 Inhibitor MK-8776 Restores the Sensitivity of Chemotherapeutics in P-glycoprotein Overexpressing Cancer Cells. Int J Mol Sci. 2019 Aug 22;20(17):4095. doi: 10.3390/ijms20174095. PMID: 31443367; PMCID: PMC6747525. 3. Montano R, Khan N, Hou H, Seigne J, Ernstoff MS, Lewis LD, Eastman A. Cell cycle perturbation induced by gemcitabine in human tumor cells in cell culture, xenografts and bladder cancer patients: implications for clinical trial designs combining gemcitabine with a Chk1 inhibitor. Oncotarget. 2017 Jun 28;8(40):67754-67768. doi: 10.18632/oncotarget.18834. PMID: 28978069; PMCID: PMC5620209. 4. Zhou ZR, Yang ZZ, Wang SJ, Zhang L, Luo JR, Feng Y, Yu XL, Chen XX, Guo XM. The Chk1 inhibitor MK-8776 increases the radiosensitivity of human triple-negative breast cancer by inhibiting autophagy. Acta Pharmacol Sin. 2017 Apr;38(4):513-523. doi: 10.1038/aps.2016.136. Epub 2017 Jan 2. PMID: 28042876; PMCID: PMC5386307.

In vitro protocol:

In vivo protocol:

1. Montano R, Khan N, Hou H, Seigne J, Ernstoff MS, Lewis LD, Eastman A. Cell cycle perturbation induced by gemcitabine in human tumor cells in cell culture, xenografts and bladder cancer patients: implications for clinical trial designs combining gemcitabine with a Chk1 inhibitor. Oncotarget. 2017 Jun 28;8(40):67754-67768. doi: 10.18632/oncotarget.18834. PMID: 28978069; PMCID: PMC5620209. 2. Zhou ZR, Yang ZZ, Wang SJ, Zhang L, Luo JR, Feng Y, Yu XL, Chen XX, Guo XM. The Chk1 inhibitor MK-8776 increases the radiosensitivity of human triple-negative breast cancer by inhibiting autophagy. Acta Pharmacol Sin. 2017 Apr;38(4):513-523. doi: 10.1038/aps.2016.136. Epub 2017 Jan 2. PMID: 28042876; PMCID: PMC5386307.

1: Montano R, Chung I, Garner KM, Parry D, Eastman A. Preclinical development of the novel Chk1 inhibitor SCH900776 in combination with DNA-damaging agents and antimetabolites. Mol Cancer Ther. 2012 Feb;11(2):427-38. doi: 10.1158/1535-7163.MCT-11-0406. Epub 2011 Dec 27. PMID: 22203733; PMCID: PMC3277678. 2: Lamore SD, Kamendi HW, Scott CW, Dragan YP, Peters MF. Cellular impedance assays for predictive preclinical drug screening of kinase inhibitor cardiovascular toxicity. Toxicol Sci. 2013 Oct;135(2):402-13. doi: 10.1093/toxsci/kft167. Epub 2013 Jul 28. PMID: 23897988. 3: Zemanova J, Hylse O, Collakova J, Vesely P, Oltova A, Borsky M, Zaprazna K, Kasparkova M, Janovska P, Verner J, Kohoutek J, Dzimkova M, Bryja V, Jaskova Z, Brychtova Y, Paruch K, Trbusek M. Chk1 inhibition significantly potentiates activity of nucleoside analogs in TP53-mutated B-lymphoid cells. Oncotarget. 2016 Sep 20;7(38):62091-62106. doi: 10.18632/oncotarget.11388. PMID: 27556692; PMCID: PMC5308713. 4: David L, Fernandez-Vidal A, Bertoli S, Grgurevic S, Lepage B, Deshaies D, Prade N, Cartel M, Larrue C, Sarry JE, Delabesse E, Cazaux C, Didier C, Récher C, Manenti S, Hoffmann JS. CHK1 as a therapeutic target to bypass chemoresistance in AML. Sci Signal. 2016 Sep 13;9(445):ra90. doi: 10.1126/scisignal.aac9704. PMID: 27625304. 5: Samadder P, Suchánková T, Hylse O, Khirsariya P, Nikulenkov F, Drápela S, Straková N, Vaňhara P, Vašíčková K, Kolářová H, Binó L, Bittová M, Ovesná P, Kollár P, Fedr R, Ešner M, Jaroš J, Hampl A, Krejčí L, Paruch K, Souček K. Synthesis and Profiling of a Novel Potent Selective Inhibitor of CHK1 Kinase Possessing Unusual N-trifluoromethylpyrazole Pharmacophore Resistant to Metabolic N-dealkylation. Mol Cancer Ther. 2017 Sep;16(9):1831-1842. doi: 10.1158/1535-7163.MCT-17-0018. Epub 2017 Jun 15. PMID: 28619751. 6: Herůdková J, Paruch K, Khirsariya P, Souček K, Krkoška M, Vondálová Blanářová O, Sova P, Kozubík A, Hyršlová Vaculová A. Chk1 Inhibitor SCH900776 Effectively Potentiates the Cytotoxic Effects of Platinum-Based Chemotherapeutic Drugs in Human Colon Cancer Cells. Neoplasia. 2017 Oct;19(10):830-841. doi: 10.1016/j.neo.2017.08.002. Epub 2017 Sep 6. PMID: 28888100; PMCID: PMC5591453. 7: Drápela S, Khirsariya P, van Weerden WM, Fedr R, Suchánková T, Búzová D, Červený J, Hampl A, Puhr M, Watson WR, Culig Z, Krejčí L, Paruch K, Souček K. The CHK1 inhibitor MU380 significantly increases the sensitivity of human docetaxel-resistant prostate cancer cells to gemcitabine through the induction of mitotic catastrophe. Mol Oncol. 2020 Oct;14(10):2487-2503. doi: 10.1002/1878-0261.12756. Epub 2020 Jul 16. PMID: 32579780; PMCID: PMC7530791. 8: Krkoška M, Paruch K, Šošolíková T, Vázquez-Gómez G, Herůdková J, Novotný J, Ovesná P, Sova P, Hyršlová Vaculová A. Inhibition of Chk1 stimulates cytotoxic action of platinum-based drugs and TRAIL combination in human prostate cancer cells. Biol Chem. 2024 Mar 8;405(6):395-406. doi: 10.1515/hsz-2023-0111. PMID: 38452398.