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Details

Stereochemistry ABSOLUTE
Molecular Formula C17H16ClN3O
Molecular Weight 313.781
Optical Activity UNSPECIFIED
Defined Stereocenters 1 / 1
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of AT-13148

SMILES

NC[C@@](O)(C1=CC=C(Cl)C=C1)C2=CC=C(C=C2)C3=CNN=C3

InChI

InChIKey=IIRWNGPLJQXWFJ-KRWDZBQOSA-N
InChI=1S/C17H16ClN3O/c18-16-7-5-15(6-8-16)17(22,11-19)14-3-1-12(2-4-14)13-9-20-21-10-13/h1-10,22H,11,19H2,(H,20,21)/t17-/m0/s1

HIDE SMILES / InChI

Molecular Formula C17H16ClN3O
Molecular Weight 313.781
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 1 / 1
E/Z Centers 0
Optical Activity UNSPECIFIED

Description
Curator's Comment: Description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/22781553

AT13148, being developed by Astex Pharmaceuticals and its collaborators, is an orally active small molecule inhibitor of Rho activated kinases (ROCK) 1 and 2 and of protein kinase (PK) A and is currently in phase 1 clinical studies under Cancer Research UK’s Clinical Development Program (CDP). AT13148 is currently being tested in a phase 1 clinical trial in patients with advanced solid tumors.

Approval Year

Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
400 nM
160 mg single, oral
dose: 160 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
AT-13148 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
120 nM
40 mg single, oral
dose: 40 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
AT-13148 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
700 nM
300 mg single, oral
dose: 300 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
AT-13148 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
50 nM
20 mg 1 times / day multiple, oral
dose: 20 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
AT-13148 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
400 nM
180 mg single, oral
dose: 180 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
AT-13148 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
20 nM
5 mg single, oral
dose: 5 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
AT-13148 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
20000 nM × h
160 mg single, oral
dose: 160 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
AT-13148 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
2100 nM × h
40 mg single, oral
dose: 40 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
AT-13148 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
40000 nM × h
300 mg single, oral
dose: 300 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
AT-13148 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
20000 nM × h
180 mg single, oral
dose: 180 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
AT-13148 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
900 nM × h
5 mg single, oral
dose: 5 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
AT-13148 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
40 h
160 mg single, oral
dose: 160 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
AT-13148 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
15 h
40 mg single, oral
dose: 40 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
AT-13148 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
60 h
300 mg single, oral
dose: 300 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
AT-13148 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
24 h
20 mg 1 times / day multiple, oral
dose: 20 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
AT-13148 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
40 h
180 mg single, oral
dose: 180 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
AT-13148 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
60 h
5 mg single, oral
dose: 5 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
AT-13148 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse events​
240 mg 3 times / week multiple, oral
Highest studied dose
Dose: 240 mg, 3 times / week
Route: oral
Route: multiple
Dose: 240 mg, 3 times / week
Sources: Page: p.4778
unhealthy, 34–76
n = 6
Health Status: unhealthy
Condition: Cancer
Age Group: 34–76
Sex: M+F
Population Size: 6
Sources: Page: p.4778
DLT: Elevated liver enzymes...
Dose limiting toxicities:
Elevated liver enzymes (16.7%)
Sources: Page: p.4778
240 mg 3 times / week multiple, oral (max)
Highest studied dose
Dose: 240 mg, 3 times / week
Route: oral
Route: multiple
Dose: 240 mg, 3 times / week
Sources: Page: p.4778
unhealthy, 34–76
n = 7
Health Status: unhealthy
Condition: Cancer
Age Group: 34–76
Sex: M+F
Population Size: 7
Sources: Page: p.4778
DLT: Pneumonitis...
Dose limiting toxicities:
Pneumonitis (grade 3, 14.3%)
Sources: Page: p.4778
300 mg 3 times / week multiple, oral
Highest studied dose
Dose: 300 mg, 3 times / week
Route: oral
Route: multiple
Dose: 300 mg, 3 times / week
Sources: Page: p.4778
unhealthy, 34–76
n = 5
Health Status: unhealthy
Condition: Cancer
Age Group: 34–76
Sex: M+F
Population Size: 5
Sources: Page: p.4778
DLT: Hypotension, Hypotension...
Other AEs: Hypotension...
Dose limiting toxicities:
Hypotension (grade 3, 20%)
Hypotension (grade 4, 20%)
Other AEs:
Hypotension (grade 2, 40%)
Sources: Page: p.4778
180 mg 3 times / week multiple, oral
MTD
Dose: 180 mg, 3 times / week
Route: oral
Route: multiple
Dose: 180 mg, 3 times / week
Sources: Page: p.4778
unhealthy, 34–76
n = 7
Health Status: unhealthy
Condition: Cancer
Age Group: 34–76
Sex: M+F
Population Size: 7
Sources: Page: p.4778
DLT: Maculopapular rash...
Dose limiting toxicities:
Maculopapular rash (grade 3, 14.3%)
Sources: Page: p.4778
AEs

AEs

AESignificanceDosePopulation
Elevated liver enzymes 16.7%
DLT
240 mg 3 times / week multiple, oral
Highest studied dose
Dose: 240 mg, 3 times / week
Route: oral
Route: multiple
Dose: 240 mg, 3 times / week
Sources: Page: p.4778
unhealthy, 34–76
n = 6
Health Status: unhealthy
Condition: Cancer
Age Group: 34–76
Sex: M+F
Population Size: 6
Sources: Page: p.4778
Pneumonitis grade 3, 14.3%
DLT
240 mg 3 times / week multiple, oral (max)
Highest studied dose
Dose: 240 mg, 3 times / week
Route: oral
Route: multiple
Dose: 240 mg, 3 times / week
Sources: Page: p.4778
unhealthy, 34–76
n = 7
Health Status: unhealthy
Condition: Cancer
Age Group: 34–76
Sex: M+F
Population Size: 7
Sources: Page: p.4778
Hypotension grade 2, 40%
300 mg 3 times / week multiple, oral
Highest studied dose
Dose: 300 mg, 3 times / week
Route: oral
Route: multiple
Dose: 300 mg, 3 times / week
Sources: Page: p.4778
unhealthy, 34–76
n = 5
Health Status: unhealthy
Condition: Cancer
Age Group: 34–76
Sex: M+F
Population Size: 5
Sources: Page: p.4778
Hypotension grade 3, 20%
DLT
300 mg 3 times / week multiple, oral
Highest studied dose
Dose: 300 mg, 3 times / week
Route: oral
Route: multiple
Dose: 300 mg, 3 times / week
Sources: Page: p.4778
unhealthy, 34–76
n = 5
Health Status: unhealthy
Condition: Cancer
Age Group: 34–76
Sex: M+F
Population Size: 5
Sources: Page: p.4778
Hypotension grade 4, 20%
DLT
300 mg 3 times / week multiple, oral
Highest studied dose
Dose: 300 mg, 3 times / week
Route: oral
Route: multiple
Dose: 300 mg, 3 times / week
Sources: Page: p.4778
unhealthy, 34–76
n = 5
Health Status: unhealthy
Condition: Cancer
Age Group: 34–76
Sex: M+F
Population Size: 5
Sources: Page: p.4778
Maculopapular rash grade 3, 14.3%
DLT
180 mg 3 times / week multiple, oral
MTD
Dose: 180 mg, 3 times / week
Route: oral
Route: multiple
Dose: 180 mg, 3 times / week
Sources: Page: p.4778
unhealthy, 34–76
n = 7
Health Status: unhealthy
Condition: Cancer
Age Group: 34–76
Sex: M+F
Population Size: 7
Sources: Page: p.4778
Sourcing

Sourcing

Vendor/AggregatorIDURL
PubMed

PubMed

TitleDatePubMed
Role of the anti-glioma drug AT13148 in the inhibition of Notch signaling pathway.
2015 Nov 15
AT13148, a first-in-class multi-AGC kinase inhibitor, potently inhibits gastric cancer cells both in vitro and in vivo.
2016 Sep 9
Patents

Patents

Sample Use Guides

Mice: 50 mg/kg p.o.
Route of Administration: Oral
Screening of AT-13148 against a panel of kinases at 10 umol/L revealed >80% inhibition of the structurally related AGC kinases AKT, PKA, ROCK2, p70S6K, MSK, RSK1/2, and SGK
Substance Class Chemical
Created
by admin
on Sat Dec 16 08:37:14 GMT 2023
Edited
by admin
on Sat Dec 16 08:37:14 GMT 2023
Record UNII
A49037RP1E
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
AT-13148
Common Name English
BENZENEMETHANOL, .ALPHA.-(AMINOMETHYL)-.ALPHA.-(4-CHLOROPHENYL)-4-(1H-PYRAZOL-4-YL)-, (.ALPHA.S)-
Systematic Name English
(S)-1-(4-(1H-PYRAZOL-4-YL)PHENYL)-2-AMINO-1-(4-CHLOROPHENYL)ETHANOL
Systematic Name English
AT13148
Code English
(+)-(S)-2-AMINO-1-(4-CHLOROPHENYL)-1-(4-(1H-PYRAZOL-4-YL)PHENYL)ETHANOL
Systematic Name English
Code System Code Type Description
NCI_THESAURUS
C101786
Created by admin on Sat Dec 16 08:37:14 GMT 2023 , Edited by admin on Sat Dec 16 08:37:14 GMT 2023
PRIMARY
PUBCHEM
24905401
Created by admin on Sat Dec 16 08:37:14 GMT 2023 , Edited by admin on Sat Dec 16 08:37:14 GMT 2023
PRIMARY
SMS_ID
100000166972
Created by admin on Sat Dec 16 08:37:14 GMT 2023 , Edited by admin on Sat Dec 16 08:37:14 GMT 2023
PRIMARY
EVMPD
SUB181270
Created by admin on Sat Dec 16 08:37:14 GMT 2023 , Edited by admin on Sat Dec 16 08:37:14 GMT 2023
PRIMARY
ChEMBL
CHEMBL3544960
Created by admin on Sat Dec 16 08:37:14 GMT 2023 , Edited by admin on Sat Dec 16 08:37:14 GMT 2023
PRIMARY
CAS
1056901-62-2
Created by admin on Sat Dec 16 08:37:14 GMT 2023 , Edited by admin on Sat Dec 16 08:37:14 GMT 2023
PRIMARY
FDA UNII
A49037RP1E
Created by admin on Sat Dec 16 08:37:14 GMT 2023 , Edited by admin on Sat Dec 16 08:37:14 GMT 2023
PRIMARY
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