MK-0752

Possibly Marketed Outside US

Details

Stereochemistry	ACHIRAL
Molecular Formula	C21H21ClF2O4S
Molecular Weight	442.904
Optical Activity	UNSPECIFIED
Defined Stereocenters	2 / 2
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

OC(=O)CC[C@H]1CC[C@@](CC1)(C2=C(F)C=CC(F)=C2)S(=O)(=O)C3=CC=C(Cl)C=C3

InChI

InChIKey=XCGJIFAKUZNNOR-QCKZDCLWSA-N

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+

HIDE SMILES / InChI

Molecular Formula	C21H21ClF2O4S
Molecular Weight	442.904
Charge	0
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	2 / 2
E/Z Centers	0
Optical Activity	UNSPECIFIED

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/26704638 | https://www.ncbi.nlm.nih.gov/pubmed/29438372 | https://clinicaltrials.gov/ct2/show/NCT00645333

MK-0752 is a potent, reversible inhibitor of γ-secretase, which inhibits γ-secretase to cleave substrates such as amyloid precursor protein. MK-0752 shows promising effects on inhibiting the growth of several types of cancer cells and was investigated in clinical trials for cancer treatment. For example in ovarian cancer models MK-0752 alone actively induced cell growth inhibition, G2/M phase cell cycle arrest and apoptosis with down-regulation of Notch1 and its downstream effectors in a dose- and time-dependent manner. Moreover, the sequential combination of cisplatin prior to MK-0752 significantly promoted cell apoptosis and inhibited the subcutaneous xenograft growth of ovarian cancer in nude mice. Through its effects on the Notch pathway, MK-0752 reduces the number of breast cancer stem cells in tumorgrafts, enhancing the efficacy of the chemotherapy drug docetaxel in mice with breast cancer tumors. Unfortunately, in phase II clinical trials MK-0752 failed to demonstrate efficacy.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Gamma-secretase 21 Target ID: CHEMBL2094135 Sources: https://www.ncbi.nlm.nih.gov/pubmed/20463236	Inhibitor 8504

C_max

Value	Dose	Analyte	Population
68 μM EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22547604/	450 mg single, oral dose: 450 mg route of administration: Oral experiment type: SINGLE co-administered:	MK-0752 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
54.9 μM EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22547604/	600 mg single, oral dose: 600 mg route of administration: Oral experiment type: SINGLE co-administered:	MK-0752 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
95.9 μM EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22547604/	450 mg 1 times / day multiple, oral dose: 450 mg route of administration: Oral experiment type: MULTIPLE co-administered:	MK-0752 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
92.3 μM EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22547604/	600 mg 1 times / day multiple, oral dose: 600 mg route of administration: Oral experiment type: MULTIPLE co-administered:	MK-0752 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
56 μM EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22547604/	450 mg single, oral dose: 450 mg route of administration: Oral experiment type: SINGLE co-administered:	MK-0752 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
72.5 μM EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22547604/	600 mg single, oral dose: 600 mg route of administration: Oral experiment type: SINGLE co-administered:	MK-0752 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
47.2 μM EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22547604/	450 mg 1 times / day multiple, oral dose: 450 mg route of administration: Oral experiment type: MULTIPLE co-administered:	MK-0752 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
84.5 μM EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22547604/	600 mg 1 times / day multiple, oral dose: 600 mg route of administration: Oral experiment type: MULTIPLE co-administered:	MK-0752 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
190 μM EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22547604/	1800 mg single, oral dose: 1800 mg route of administration: Oral experiment type: SINGLE co-administered:	MK-0752 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
166.2 μM EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22547604/	2400 mg single, oral dose: 2400 mg route of administration: Oral experiment type: SINGLE co-administered:	MK-0752 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
281.4 μM EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22547604/	3200 mg single, oral dose: 3200 mg route of administration: Oral experiment type: SINGLE co-administered:	MK-0752 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
413 μM EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22547604/	4200 mg single, oral dose: 4200 mg route of administration: Oral experiment type: SINGLE co-administered:	MK-0752 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
183.3 μM EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22547604/	1800 mg 1 times / week multiple, oral dose: 1800 mg route of administration: Oral experiment type: MULTIPLE co-administered:	MK-0752 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
162.6 μM EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22547604/	2400 mg 1 times / week multiple, oral dose: 2400 mg route of administration: Oral experiment type: MULTIPLE co-administered:	MK-0752 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
273.4 μM EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22547604/	3200 mg 1 times / week multiple, oral dose: 3200 mg route of administration: Oral experiment type: MULTIPLE co-administered:	MK-0752 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
374.7 μM EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22547604/	4200 mg 1 times / week multiple, oral dose: 4200 mg route of administration: Oral experiment type: MULTIPLE co-administered:	MK-0752 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

AUC

Value	Dose	Analyte	Population
935 μM × h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22547604/	450 mg single, oral dose: 450 mg route of administration: Oral experiment type: SINGLE co-administered:	MK-0752 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
962 μM × h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22547604/	600 mg single, oral dose: 600 mg route of administration: Oral experiment type: SINGLE co-administered:	MK-0752 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
1504 μM × h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22547604/	450 mg 1 times / day multiple, oral dose: 450 mg route of administration: Oral experiment type: MULTIPLE co-administered:	MK-0752 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
1719 μM × h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22547604/	600 mg 1 times / day multiple, oral dose: 600 mg route of administration: Oral experiment type: MULTIPLE co-administered:	MK-0752 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
761 μM × h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22547604/	450 mg single, oral dose: 450 mg route of administration: Oral experiment type: SINGLE co-administered:	MK-0752 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
1213 μM × h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22547604/	600 mg single, oral dose: 600 mg route of administration: Oral experiment type: SINGLE co-administered:	MK-0752 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
758 μM × h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22547604/	450 mg 1 times / day multiple, oral dose: 450 mg route of administration: Oral experiment type: MULTIPLE co-administered:	MK-0752 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
1342 μM × h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22547604/	600 mg 1 times / day multiple, oral dose: 600 mg route of administration: Oral experiment type: MULTIPLE co-administered:	MK-0752 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
3084 μM × h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22547604/	1800 mg single, oral dose: 1800 mg route of administration: Oral experiment type: SINGLE co-administered:	MK-0752 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
2747 μM × h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22547604/	2400 mg single, oral dose: 2400 mg route of administration: Oral experiment type: SINGLE co-administered:	MK-0752 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
4515 μM × h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22547604/	3200 mg single, oral dose: 3200 mg route of administration: Oral experiment type: SINGLE co-administered:	MK-0752 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
6228 μM × h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22547604/	4200 mg single, oral dose: 4200 mg route of administration: Oral experiment type: SINGLE co-administered:	MK-0752 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
3168 μM × h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22547604/	1800 mg 1 times / week multiple, oral dose: 1800 mg route of administration: Oral experiment type: MULTIPLE co-administered:	MK-0752 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
2921 μM × h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22547604/	2400 mg 1 times / week multiple, oral dose: 2400 mg route of administration: Oral experiment type: MULTIPLE co-administered:	MK-0752 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
4646 μM × h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22547604/	3200 mg 1 times / week multiple, oral dose: 3200 mg route of administration: Oral experiment type: MULTIPLE co-administered:	MK-0752 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
6316 μM × h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22547604/	4200 mg 1 times / week multiple, oral dose: 4200 mg route of administration: Oral experiment type: MULTIPLE co-administered:	MK-0752 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

T_1/2

Value	Dose	Analyte	Population
15.1 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22547604/	450 mg single, oral dose: 450 mg route of administration: Oral experiment type: SINGLE co-administered:	MK-0752 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
21.2 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22547604/	600 mg single, oral dose: 600 mg route of administration: Oral experiment type: SINGLE co-administered:	MK-0752 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
16.2 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22547604/	450 mg 1 times / day multiple, oral dose: 450 mg route of administration: Oral experiment type: MULTIPLE co-administered:	MK-0752 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
22.1 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22547604/	600 mg 1 times / day multiple, oral dose: 600 mg route of administration: Oral experiment type: MULTIPLE co-administered:	MK-0752 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
15 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22547604/	450 mg single, oral dose: 450 mg route of administration: Oral experiment type: SINGLE co-administered:	MK-0752 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
30 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22547604/	600 mg single, oral dose: 600 mg route of administration: Oral experiment type: SINGLE co-administered:	MK-0752 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
12.3 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22547604/	450 mg 1 times / day multiple, oral dose: 450 mg route of administration: Oral experiment type: MULTIPLE co-administered:	MK-0752 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
15.8 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22547604/	600 mg 1 times / day multiple, oral dose: 600 mg route of administration: Oral experiment type: MULTIPLE co-administered:	MK-0752 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
13.8 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22547604/	1800 mg single, oral dose: 1800 mg route of administration: Oral experiment type: SINGLE co-administered:	MK-0752 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
16.2 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22547604/	2400 mg single, oral dose: 2400 mg route of administration: Oral experiment type: SINGLE co-administered:	MK-0752 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
17.8 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22547604/	3200 mg single, oral dose: 3200 mg route of administration: Oral experiment type: SINGLE co-administered:	MK-0752 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
15.6 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22547604/	4200 mg single, oral dose: 4200 mg route of administration: Oral experiment type: SINGLE co-administered:	MK-0752 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
13.8 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22547604/	1800 mg 1 times / week multiple, oral dose: 1800 mg route of administration: Oral experiment type: MULTIPLE co-administered:	MK-0752 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
15.6 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22547604/	2400 mg 1 times / week multiple, oral dose: 2400 mg route of administration: Oral experiment type: MULTIPLE co-administered:	MK-0752 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
13.1 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22547604/	3200 mg 1 times / week multiple, oral dose: 3200 mg route of administration: Oral experiment type: MULTIPLE co-administered:	MK-0752 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
15.4 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22547604/	4200 mg 1 times / week multiple, oral dose: 4200 mg route of administration: Oral experiment type: MULTIPLE co-administered:	MK-0752 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

PubMed

Title	Date	PubMed
Determination of the gamma-secretase inhibitor MK-0752 in human plasma by online extraction and electrospray tandem mass spectrometry (HTLC-ESI-MS/MS).	2010-09-01	20702149
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.	2008-02-15	18249589

Patents

Sample Use Guides

In Vivo Use Guide

MK-0752 in escalating doses of 300, 450, 600, and 800 mg given orally on days 1-3, followed by docetaxel 80 mg/m2 day 8 and pegfilgrastim 6 mg SQ on day 9

Route of Administration: Oral

Substance Class	Chemical Created by `admin` on `Mon Mar 31 21:26:04 GMT 2025` Edited by `admin` on `Mon Mar 31 21:26:04 GMT 2025`
Record UNII	9JD9B4S53T
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

CYCLOHEXANEPROPANOIC ACID, 4-((4-CHLOROPHENYL)SULFONYL)-4-(2,5-DIFLUOROPHENYL)-, CIS-

Preferred Name

English

MK-0752

Common Name

English

Code System Code Type Description

FDA UNII

9JD9B4S53T