Details
| Stereochemistry | ACHIRAL |
| Molecular Formula | C21H20ClF2O4S.Na |
| Molecular Weight | 464.886 |
| Optical Activity | UNSPECIFIED |
| Defined Stereocenters | 2 / 2 |
| E/Z Centers | 0 |
| Charge | 0 |
SHOW SMILES / InChI
SMILES
[Na+].[O-]C(=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=WFPVQMLUYJLUCN-YQEPSNHFSA-M
InChI=1S/C21H21ClF2O4S.Na/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);/q;+1/p-1/t14-,21+;
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.
Approval Year
Cmax
| Value | Dose | Co-administered | 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 | Co-administered | 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 |
T1/2
| Value | Dose | Co-administered | 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 |
|
| 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 |
Patents
| Name | Type | Language | ||
|---|---|---|---|---|
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Preferred Name | English | ||
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Common Name | English |
| Code System | Code | Type | Description | ||
|---|---|---|---|---|---|
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656810-87-6
Created by
admin on Mon Mar 31 18:32:48 GMT 2025 , Edited by admin on Mon Mar 31 18:32:48 GMT 2025
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PRIMARY | |||
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23678619
Created by
admin on Mon Mar 31 18:32:48 GMT 2025 , Edited by admin on Mon Mar 31 18:32:48 GMT 2025
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PRIMARY | |||
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01HO73LPA0
Created by
admin on Mon Mar 31 18:32:48 GMT 2025 , Edited by admin on Mon Mar 31 18:32:48 GMT 2025
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PRIMARY |
ACTIVE MOIETY
SUBSTANCE RECORD
