Details
Stereochemistry | ACHIRAL |
Molecular Formula | C25H21N5O.ClH |
Molecular Weight | 443.928 |
Optical Activity | NONE |
Defined Stereocenters | 0 / 0 |
E/Z Centers | 0 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
Cl.NC1(CCC1)C2=CC=C(C=C2)C3=NC4=C(C=C3C5=CC=CC=C5)C6=NNC(=O)N6C=C4
InChI
InChIKey=LFYOZCBFOSSLNJ-UHFFFAOYSA-N
InChI=1S/C25H21N5O.ClH/c26-25(12-4-13-25)18-9-7-17(8-10-18)22-19(16-5-2-1-3-6-16)15-20-21(27-22)11-14-30-23(20)28-29-24(30)31;/h1-3,5-11,14-15H,4,12-13,26H2,(H,29,31);1H
Molecular Formula | C25H21N5O |
Molecular Weight | 407.4671 |
Charge | 0 |
Count |
|
Stereochemistry | ACHIRAL |
Additional Stereochemistry | No |
Defined Stereocenters | 0 / 0 |
E/Z Centers | 0 |
Optical Activity | NONE |
Molecular Formula | ClH |
Molecular Weight | 36.461 |
Charge | 0 |
Count |
|
Stereochemistry | ACHIRAL |
Additional Stereochemistry | No |
Defined Stereocenters | 0 / 0 |
E/Z Centers | 0 |
Optical Activity | NONE |
DescriptionCurator's Comment: description was created based on several sources, including:
http://adisinsight.springer.com/drugs/800028810 | http://www.pharmacodia.com/yaodu/html/v1/chemicals/cddaa6e1ad5ba4c70c6c05db38099fa0.html | https://en.wikipedia.org/wiki/MK-2206 | https://www.ncbi.nlm.nih.gov/pubmed/20571069
Curator's Comment: description was created based on several sources, including:
http://adisinsight.springer.com/drugs/800028810 | http://www.pharmacodia.com/yaodu/html/v1/chemicals/cddaa6e1ad5ba4c70c6c05db38099fa0.html | https://en.wikipedia.org/wiki/MK-2206 | https://www.ncbi.nlm.nih.gov/pubmed/20571069
MK-2206 is an oral selective allosteric inhibitor of Akt that targets all three isoforms of human Akt (Akt-1, Akt-2 and Akt-3). In a phase I study of solid tumors, MK-2206 demonstrated evidence of target modulation and anti-proliferative activity as a single agent and in combination with other agents. Current ongoing trials of MK-2206 include monotherapy and combination therapy in breast cancer, colorectal cancer, haematological malignancies, non-small cell lung cancer and other. Detected treatment-related adverse event are: rash, fatigue, hyperglycemia.
CNS Activity
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
Target ID: CHEMBL4282 Sources: https://www.ncbi.nlm.nih.gov/pubmed/20571069 |
5.0 nM [IC50] | ||
Target ID: CHEMBL2431 Sources: https://www.ncbi.nlm.nih.gov/pubmed/20571069 |
12.0 nM [IC50] | ||
Target ID: CHEMBL4816 Sources: https://www.ncbi.nlm.nih.gov/pubmed/20571069 |
65.0 nM [IC50] |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
---|---|---|---|---|
Primary | Unknown Approved UseUnknown |
|||
Primary | Unknown Approved UseUnknown |
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Primary | Unknown Approved UseUnknown |
Cmax
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
264 nM EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/25239610 |
200 mg 1 times / week single, oral dose: 200 mg route of administration: Oral experiment type: SINGLE co-administered: |
MK-2206 plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
|
345 nM EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/25239610 |
200 mg 1 times / week multiple, oral dose: 200 mg route of administration: Oral experiment type: MULTIPLE co-administered: |
MK-2206 plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
|
466 nM EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/25239610 |
300 mg single, oral dose: 300 mg route of administration: Oral experiment type: SINGLE co-administered: |
MK-2206 plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
|
66.4 nM EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22025163 |
60 mg single, oral dose: 60 mg route of administration: Oral experiment type: SINGLE co-administered: |
MK-2206 plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
|
132 nM EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22025163 |
90 mg single, oral dose: 90 mg route of administration: Oral experiment type: SINGLE co-administered: |
MK-2206 plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
|
163 nM EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22025163 |
60 mg 1 times / 2 days multiple, oral dose: 60 mg route of administration: Oral experiment type: MULTIPLE co-administered: |
MK-2206 plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
|
232 nM EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22025163 |
90 mg 1 times / 2 days multiple, oral dose: 90 mg route of administration: Oral experiment type: MULTIPLE co-administered: |
MK-2206 plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
AUC
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
16400 nM × h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/25239610 |
200 mg 1 times / week single, oral dose: 200 mg route of administration: Oral experiment type: SINGLE co-administered: |
MK-2206 plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
|
23500 nM × h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/25239610 |
200 mg 1 times / week multiple, oral dose: 200 mg route of administration: Oral experiment type: MULTIPLE co-administered: |
MK-2206 plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
|
27700 nM × h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/25239610 |
300 mg single, oral dose: 300 mg route of administration: Oral experiment type: SINGLE co-administered: |
MK-2206 plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
|
1820 nM × h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22025163 |
60 mg single, oral dose: 60 mg route of administration: Oral experiment type: SINGLE co-administered: |
MK-2206 plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
|
3950 nM × h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22025163 |
90 mg single, oral dose: 90 mg route of administration: Oral experiment type: SINGLE co-administered: |
MK-2206 plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
|
5860 nM × h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22025163 |
60 mg 1 times / 2 days multiple, oral dose: 60 mg route of administration: Oral experiment type: MULTIPLE co-administered: |
MK-2206 plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
|
7970 nM × h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22025163 |
90 mg 1 times / 2 days multiple, oral dose: 90 mg route of administration: Oral experiment type: MULTIPLE co-administered: |
MK-2206 plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
T1/2
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
75.1 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/25239610 |
200 mg 1 times / week multiple, oral dose: 200 mg route of administration: Oral experiment type: MULTIPLE co-administered: |
MK-2206 plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
|
71.3 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22025163 |
60 mg 1 times / 2 days multiple, oral dose: 60 mg route of administration: Oral experiment type: MULTIPLE co-administered: |
MK-2206 plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
|
66.2 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22025163 |
90 mg 1 times / 2 days multiple, oral dose: 90 mg route of administration: Oral experiment type: MULTIPLE co-administered: |
MK-2206 plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
Doses
Dose | Population | Adverse events |
---|---|---|
300 mg 1 times / week multiple, oral Highest studied dose Dose: 300 mg, 1 times / week Route: oral Route: multiple Dose: 300 mg, 1 times / week Sources: Page: p.5, 25 |
unhealthy, ADULT n = 3 Health Status: unhealthy Condition: cancer Age Group: ADULT Sex: M+F Food Status: FASTED Population Size: 3 Sources: Page: p.5, 25 |
DLT: Skin rash... Dose limiting toxicities: Skin rash (grade 3, 100%) Sources: Page: p.5, 25 |
200 mg 1 times / week multiple, oral MTD Dose: 200 mg, 1 times / week Route: oral Route: multiple Dose: 200 mg, 1 times / week Sources: Page: p.5, 25 |
unhealthy, ADULT n = 17 Health Status: unhealthy Condition: cancer Age Group: ADULT Sex: M+F Food Status: FASTED Population Size: 17 Sources: Page: p.5, 25 |
DLT: Skin rash, Dermatitis acneiform... Dose limiting toxicities: Skin rash (grade 3, 17.6%) Sources: Page: p.5, 25Dermatitis acneiform (grade 3, 5.9%) |
60 mg 1 times / 2 days multiple, oral MTD Dose: 60 mg, 1 times / 2 days Route: oral Route: multiple Dose: 60 mg, 1 times / 2 days Sources: Page: p.4690 |
unhealthy, ADULT n = 20 Health Status: unhealthy Condition: cancer Age Group: ADULT Sex: M+F Food Status: FASTED Population Size: 20 Sources: Page: p.4690 |
DLT: Erythematous rash... Dose limiting toxicities: Erythematous rash (grade 3, 5%) Sources: Page: p.4690 |
60 mg 1 times / 2 days multiple, oral MTD Dose: 60 mg, 1 times / 2 days Route: oral Route: multiple Dose: 60 mg, 1 times / 2 days Sources: Page: sup. table1 |
unhealthy, ADULT n = 38 Health Status: unhealthy Condition: cancer Age Group: ADULT Sex: M+F Food Status: FASTED Population Size: 38 Sources: Page: sup. table1 |
DLT: Stomatitis, Skin rash... Dose limiting toxicities: Stomatitis (grade 3, 2.6%) Sources: Page: sup. table1Skin rash (grade 3, 2.6%) Skin rash (grade 3, 18.4%) Skin rash (grade 3, 5.3%) |
90 mg 1 times / 2 days multiple, oral Studied dose Dose: 90 mg, 1 times / 2 days Route: oral Route: multiple Dose: 90 mg, 1 times / 2 days Sources: Page: p.4690 |
unhealthy, ADULT n = 7 Health Status: unhealthy Condition: cancer Age Group: ADULT Sex: M+F Food Status: FASTED Population Size: 7 Sources: Page: p.4690 |
DLT: Stomatitis, Erythematous rash... Dose limiting toxicities: Stomatitis (grade 3, 14.3%) Sources: Page: p.4690Erythematous rash (grade 3-4, 57.1%) |
AEs
AE | Significance | Dose | Population |
---|---|---|---|
Skin rash | grade 3, 100% DLT |
300 mg 1 times / week multiple, oral Highest studied dose Dose: 300 mg, 1 times / week Route: oral Route: multiple Dose: 300 mg, 1 times / week Sources: Page: p.5, 25 |
unhealthy, ADULT n = 3 Health Status: unhealthy Condition: cancer Age Group: ADULT Sex: M+F Food Status: FASTED Population Size: 3 Sources: Page: p.5, 25 |
Skin rash | grade 3, 17.6% DLT |
200 mg 1 times / week multiple, oral MTD Dose: 200 mg, 1 times / week Route: oral Route: multiple Dose: 200 mg, 1 times / week Sources: Page: p.5, 25 |
unhealthy, ADULT n = 17 Health Status: unhealthy Condition: cancer Age Group: ADULT Sex: M+F Food Status: FASTED Population Size: 17 Sources: Page: p.5, 25 |
Dermatitis acneiform | grade 3, 5.9% DLT |
200 mg 1 times / week multiple, oral MTD Dose: 200 mg, 1 times / week Route: oral Route: multiple Dose: 200 mg, 1 times / week Sources: Page: p.5, 25 |
unhealthy, ADULT n = 17 Health Status: unhealthy Condition: cancer Age Group: ADULT Sex: M+F Food Status: FASTED Population Size: 17 Sources: Page: p.5, 25 |
Erythematous rash | grade 3, 5% DLT |
60 mg 1 times / 2 days multiple, oral MTD Dose: 60 mg, 1 times / 2 days Route: oral Route: multiple Dose: 60 mg, 1 times / 2 days Sources: Page: p.4690 |
unhealthy, ADULT n = 20 Health Status: unhealthy Condition: cancer Age Group: ADULT Sex: M+F Food Status: FASTED Population Size: 20 Sources: Page: p.4690 |
Skin rash | grade 3, 18.4% DLT, Disc. AE |
60 mg 1 times / 2 days multiple, oral MTD Dose: 60 mg, 1 times / 2 days Route: oral Route: multiple Dose: 60 mg, 1 times / 2 days Sources: Page: sup. table1 |
unhealthy, ADULT n = 38 Health Status: unhealthy Condition: cancer Age Group: ADULT Sex: M+F Food Status: FASTED Population Size: 38 Sources: Page: sup. table1 |
Stomatitis | grade 3, 2.6% DLT |
60 mg 1 times / 2 days multiple, oral MTD Dose: 60 mg, 1 times / 2 days Route: oral Route: multiple Dose: 60 mg, 1 times / 2 days Sources: Page: sup. table1 |
unhealthy, ADULT n = 38 Health Status: unhealthy Condition: cancer Age Group: ADULT Sex: M+F Food Status: FASTED Population Size: 38 Sources: Page: sup. table1 |
Skin rash | grade 3, 2.6% DLT, Disc. AE |
60 mg 1 times / 2 days multiple, oral MTD Dose: 60 mg, 1 times / 2 days Route: oral Route: multiple Dose: 60 mg, 1 times / 2 days Sources: Page: sup. table1 |
unhealthy, ADULT n = 38 Health Status: unhealthy Condition: cancer Age Group: ADULT Sex: M+F Food Status: FASTED Population Size: 38 Sources: Page: sup. table1 |
Skin rash | grade 3, 5.3% DLT |
60 mg 1 times / 2 days multiple, oral MTD Dose: 60 mg, 1 times / 2 days Route: oral Route: multiple Dose: 60 mg, 1 times / 2 days Sources: Page: sup. table1 |
unhealthy, ADULT n = 38 Health Status: unhealthy Condition: cancer Age Group: ADULT Sex: M+F Food Status: FASTED Population Size: 38 Sources: Page: sup. table1 |
Stomatitis | grade 3, 14.3% DLT |
90 mg 1 times / 2 days multiple, oral Studied dose Dose: 90 mg, 1 times / 2 days Route: oral Route: multiple Dose: 90 mg, 1 times / 2 days Sources: Page: p.4690 |
unhealthy, ADULT n = 7 Health Status: unhealthy Condition: cancer Age Group: ADULT Sex: M+F Food Status: FASTED Population Size: 7 Sources: Page: p.4690 |
Erythematous rash | grade 3-4, 57.1% DLT |
90 mg 1 times / 2 days multiple, oral Studied dose Dose: 90 mg, 1 times / 2 days Route: oral Route: multiple Dose: 90 mg, 1 times / 2 days Sources: Page: p.4690 |
unhealthy, ADULT n = 7 Health Status: unhealthy Condition: cancer Age Group: ADULT Sex: M+F Food Status: FASTED Population Size: 7 Sources: Page: p.4690 |
Overview
CYP3A4 | CYP2C9 | CYP2D6 | hERG |
---|---|---|---|
Drug as perpetrator
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
moder | ||||
moderate [IC50 >35 uM] | ||||
moderate [IC50 >35 uM] | ||||
moderate [IC50 >35 uM] | ||||
moderate [Inhibition 10 uM] | ||||
moderate | ||||
no | ||||
Sources: https://pubmed.ncbi.nlm.nih.gov/24387695/ |
yes |
Drug as victim
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
major |
PubMed
Title | Date | PubMed |
---|---|---|
The Akt-specific inhibitor MK2206 selectively inhibits thyroid cancer cells harboring mutations that can activate the PI3K/Akt pathway. | 2011 Apr |
|
Harnessing the PI3K/Akt/mTOR pathway in T-cell acute lymphoblastic leukemia: eliminating activity by targeting at different levels. | 2012 Aug |
|
PI3K signaling mediates diverse regulation of ATF4 expression for the survival of HK-2 cells exposed to cadmium. | 2014 Feb |
|
Effects of AKT inhibition on HGF-mediated erlotinib resistance in non-small cell lung cancer cell lines. | 2015 Apr |
|
The Akt inhibitor MK-2206 enhances the cytotoxicity of paclitaxel (Taxol) and cisplatin in ovarian cancer cells. | 2015 Jan |
Patents
Sample Use Guides
In Vivo Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/25637165
90 mg weekly (1st 28 days cycle); 135 mg weekly (2nd 28 days cycle)
Route of Administration:
Oral
In Vitro Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/20571069
MK-2206 alone more potently inhibited the cell growth of Ras wild-type (WT) cell lines (A431, HCC827, and NCI-H292; IC50s of 5.5, 4.3, and 5.2 μmol/L, respectively) as compared with Ras-mutant cell lines (NCI-H358, NCI-H23, NCI-H1299, and Calu-6; IC50s of 13.5, 14.1, 27.0, and 28.6 μmol/L, respectively), with the exception of NCI-H460, which has a PIK3CA E545K mutation (IC50, 3.4 μmol/L).
Substance Class |
Chemical
Created
by
admin
on
Edited
Fri Dec 15 19:50:57 GMT 2023
by
admin
on
Fri Dec 15 19:50:57 GMT 2023
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Record UNII |
4HA45S22ZZ
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Record Status |
Validated (UNII)
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Record Version |
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-
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Common Name | English | ||
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Common Name | English | ||
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Code | English |
Classification Tree | Code System | Code | ||
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FDA ORPHAN DRUG |
291309
Created by
admin on Fri Dec 15 19:50:57 GMT 2023 , Edited by admin on Fri Dec 15 19:50:57 GMT 2023
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Code System | Code | Type | Description | ||
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EU/3/09/695(POSITIVE)
Created by
admin on Fri Dec 15 19:50:57 GMT 2023 , Edited by admin on Fri Dec 15 19:50:57 GMT 2023
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PRIMARY | Treatment of ovarian cancer 29/11/2009 Positive | ||
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4HA45S22ZZ
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PRIMARY | |||
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67254077
Created by
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PRIMARY | |||
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100000175290
Created by
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PRIMARY | |||
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1032349-77-1
Created by
admin on Fri Dec 15 19:50:57 GMT 2023 , Edited by admin on Fri Dec 15 19:50:57 GMT 2023
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CHEMBL1079175
Created by
admin on Fri Dec 15 19:50:57 GMT 2023 , Edited by admin on Fri Dec 15 19:50:57 GMT 2023
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PRIMARY |
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