MK-0752
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MedKoo CAT#: 525670

CAS#: 471905-41-6

Description: MK0752 is a synthetic small molecule with potential antineoplastic activity. MK0752 inhibits the Notch signaling pathway, which may result in induction of growth arrest and apoptosis in tumor cells in which the Notch signaling pathway is overactivated. The Notch signaling pathway plays an important role in cell-fate determination, cell survival, and cell proliferation. Check for active clinical trials or closed clinical trials using this agent. (NCI Thesaurus).

Chemical Structure

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MK-0752
CAS# 471905-41-6
Product data Instruction

Theoretical Analysis

MedKoo Cat#: 525670
Name: MK-0752
CAS#: 471905-41-6
Chemical Formula: C21H21ClF2O4S
Exact Mass: 442.08
Molecular Weight: 442.902
Elemental Analysis: C, 56.95; H, 4.78; Cl, 8.00; F, 8.58; O, 14.45; S, 7.24

Price and Availability

Size Price Availability Quantity
100mg USD 650 2 weeks
250mg USD 1250 2 Weeks
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Synonym: Code name: MK0752. Chemical name: cis34(3chlorophenyl)sulfonyl4(25difluorophenyl)cyclohexyl propanoicacid.

IUPAC/Chemical Name: 3-((1r,4s)-4-((4-chlorophenyl)sulfonyl)-4-(2,5-difluorophenyl)cyclohexyl)propanoic acid.

InChi Key: XCGJIFAKUZNNOR-HNSKJHPRSA-N

InChi Code: InChI=1S/C21H21ClF2O4S/c22-15-2-5-17(6-3-15)29(27,28)21(18-13-16(23)4-7-19(18)24)11-9-14(10-12-21)1-8-20(25)26/h2-7,13-14H,1,8-12H2,(H,25,26)/t14-,21-

SMILES Code: O=C(O)CC[C@H]1CC[C@](C2=CC(F)=CC=C2F)(S(=O)(C3=CC=C(Cl)C=C3)=O)CC1

Appearance: Solid powder

Purity: >98%

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

More Info: MK-0752 is a potent gamma secretase inhibitor in clinical development (IC50 50 nM). Phase I clinical trials results reported in 2006 showed that MK-0752 was well-tolerated in a limited number of patients below 300 mg/m2, and further enrollment was underway to establish the MTD. Plasma concentrations of MK-0752 at all doses were sufficient to inhibit gamma secretase. (source: D. J. Deangelo, R. M. Stone, L. B. Silverman, W. Stock, E. C. Attar, I. Fearen, A. Dallob, C. Matthews, J. Stone, S. J. Freedman and J. Aster (Dana-Farber Cancer Institute, Boston, MA; University of Chicago, Chicago, IL; Massachusetts General Hospital, Boston, MA; Merck Research Laboratories, West Point, PA; Brigham and WomenÂ’s Hospital, Boston, MA, A phase I clinical trial of the notch inhibitor MK-0752 in patients with T-cell acute lymphoblastic leukemia/lymphoma (T-ALL) and other leukemias, Journal of Clinical Oncology, 2006 ASCO Annual Meeting Proceedings (Post-Meeting Edition). Vol 24, No 18S (June 20 Supplement), 2006: 6585, webpage: http://meeting.ascopubs.org/cgi/content/abstract/24/18_suppl/6585).    

Product Data:
Product Data
Instruction:
View handling instruction
Biological target: MK-0752 is a potent, orally active and specific γ-secretase inhibitor.
In vitro activity: H1975 cell viability, cell cycle progression, and migration after transfection or under Notch inhibitor MK-0752 treatment were detected through MTT assay, flow cytometer, and wound healing assay, respectively. Notch inhibitor MK-0752 inhibited the effects of overexpressed ZFP64 on H1975 cell viability, cell cycle, migration, EMT progress, and Notch pathway activation. Reference: J Recept Signal Transduct Res. 2021 Oct;41(5):457-465. https://pubmed.ncbi.nlm.nih.gov/33054540/
In vivo activity: In this study, the GSI (gamma-secretase inhibitor) MK-0752 was administered to conscious CMP rhesus monkeys in conjunction with in vivo stable-isotope-labeling, and dose-dependently reduced newly generated CNS Abeta. These results indicate that most of the CNS APP was metabolized to products other than Abeta, including C-terminal truncated forms of Abeta: 1-14, 1-15 and 1-16; this demonstrates an alternative degradation pathway for CNS amyloid precursor protein during gamma-secretase inhibition. Reference: J Neurosci. 2010 May 12;30(19):6743-50. https://pubmed.ncbi.nlm.nih.gov/20463236/

Solubility Data

Solvent Max Conc. mg/mL Max Conc. mM
Solubility
DMF 50.0 112.89
DMSO 66.3 149.77
DMSO:PBS (pH 7.2) (1:1) 0.5 1.13
Ethanol 7.5 16.93

Preparing Stock Solutions

The following data is based on the product molecular weight 442.90 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. Jiang J, Zhang J, Fu K, Zhang T. Function and mechanism exploration of zinc finger protein 64 in lung adenocarcinoma cell growth and metastasis. J Recept Signal Transduct Res. 2021 Oct;41(5):457-465. doi: 10.1080/10799893.2020.1825490. Epub 2020 Oct 15. PMID: 33054540. 2. Saltarella I, Frassanito MA, Lamanuzzi A, Brevi A, Leone P, Desantis V, Di Marzo L, Bellone M, Derudas D, Ribatti D, Chiaramonte R, Palano MT, Neri A, Mariggiò MA, Fumarulo R, Dammacco F, Racanelli V, Vacca A, Ria R. Homotypic and Heterotypic Activation of the Notch Pathway in Multiple Myeloma-Enhanced Angiogenesis: A Novel Therapeutic Target? Neoplasia. 2019 Jan;21(1):93-105. doi: 10.1016/j.neo.2018.10.011. Epub 2018 Dec 5. PMID: 30529074; PMCID: PMC6282459. 3. Chen X, Gong L, Ou R, Zheng Z, Chen J, Xie F, Huang X, Qiu J, Zhang W, Jiang Q, Yang Y, Zhu H, Shi Z, Yan X. Sequential combination therapy of ovarian cancer with cisplatin and γ-secretase inhibitor MK-0752. Gynecol Oncol. 2016 Mar;140(3):537-44. doi: 10.1016/j.ygyno.2015.12.011. Epub 2015 Dec 15. PMID: 26704638. 4. Cook JJ, Wildsmith KR, Gilberto DB, Holahan MA, Kinney GG, Mathers PD, Michener MS, Price EA, Shearman MS, Simon AJ, Wang JX, Wu G, Yarasheski KE, Bateman RJ. Acute gamma-secretase inhibition of nonhuman primate CNS shifts amyloid precursor protein (APP) metabolism from amyloid-beta production to alternative APP fragments without amyloid-beta rebound. J Neurosci. 2010 May 12;30(19):6743-50. doi: 10.1523/JNEUROSCI.1381-10.2010. PMID: 20463236; PMCID: PMC2913973.
In vitro protocol: 1. Jiang J, Zhang J, Fu K, Zhang T. Function and mechanism exploration of zinc finger protein 64 in lung adenocarcinoma cell growth and metastasis. J Recept Signal Transduct Res. 2021 Oct;41(5):457-465. doi: 10.1080/10799893.2020.1825490. Epub 2020 Oct 15. PMID: 33054540. 2. Saltarella I, Frassanito MA, Lamanuzzi A, Brevi A, Leone P, Desantis V, Di Marzo L, Bellone M, Derudas D, Ribatti D, Chiaramonte R, Palano MT, Neri A, Mariggiò MA, Fumarulo R, Dammacco F, Racanelli V, Vacca A, Ria R. Homotypic and Heterotypic Activation of the Notch Pathway in Multiple Myeloma-Enhanced Angiogenesis: A Novel Therapeutic Target? Neoplasia. 2019 Jan;21(1):93-105. doi: 10.1016/j.neo.2018.10.011. Epub 2018 Dec 5. PMID: 30529074; PMCID: PMC6282459.
In vivo protocol: 1. Chen X, Gong L, Ou R, Zheng Z, Chen J, Xie F, Huang X, Qiu J, Zhang W, Jiang Q, Yang Y, Zhu H, Shi Z, Yan X. Sequential combination therapy of ovarian cancer with cisplatin and γ-secretase inhibitor MK-0752. Gynecol Oncol. 2016 Mar;140(3):537-44. doi: 10.1016/j.ygyno.2015.12.011. Epub 2015 Dec 15. PMID: 26704638. 2. Cook JJ, Wildsmith KR, Gilberto DB, Holahan MA, Kinney GG, Mathers PD, Michener MS, Price EA, Shearman MS, Simon AJ, Wang JX, Wu G, Yarasheski KE, Bateman RJ. Acute gamma-secretase inhibition of nonhuman primate CNS shifts amyloid precursor protein (APP) metabolism from amyloid-beta production to alternative APP fragments without amyloid-beta rebound. J Neurosci. 2010 May 12;30(19):6743-50. doi: 10.1523/JNEUROSCI.1381-10.2010. PMID: 20463236; PMCID: PMC2913973.

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1: Bai F, Tagen M, Colotta C, Miller L, Fouladi M, Stewart CF. Determination of the gamma-secretase inhibitor MK-0752 in human plasma by online extraction and electrospray tandem mass spectrometry (HTLC-ESI-MS/MS). J Chromatogr B Analyt Technol Biomed Life Sci. 2010 Sep 1;878(25):2348-52. Epub 2010 Jul 30. PubMed PMID: 20702149; PubMed Central PMCID: PMC2926936.

2: Cook JJ, Wildsmith KR, Gilberto DB, Holahan MA, Kinney GG, Mathers PD, Michener MS, Price EA, Shearman MS, Simon AJ, Wang JX, Wu G, Yarasheski KE, Bateman RJ. Acute gamma-secretase inhibition of nonhuman primate CNS shifts amyloid precursor protein (APP) metabolism from amyloid-beta production to alternative APP fragments without amyloid-beta rebound. J Neurosci. 2010 May 12;30(19):6743-50. PubMed PMID: 20463236; PubMed Central PMCID: PMC2913973.

3: Matthews CZ, Woolf EJ. Determination of a novel gamma-secretase inhibitor in human plasma and cerebrospinal fluid using automated 96 well solid phase extraction and liquid chromatography/tandem mass spectrometry. J Chromatogr B Analyt Technol Biomed Life Sci. 2008 Feb 15;863(1):36-45. Epub 2008 Jan 6. PubMed PMID: 18249589.

4: Olson RE, Albright CF. Recent progress in the medicinal chemistry of gamma-secretase inhibitors. Curr Top Med Chem. 2008;8(1):17-33. Review. PubMed PMID: 18220929.