AT-13148

Investigational

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 Search

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
Sources: http://astx.com/wp-content/uploads/2016/11/ASTX_News_2013_1_16_General_Releases.pdf
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.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
cAMP-dependent protein kinase (PKA) 18 Target ID: CHEMBL2094138 Sources: http://astx.com/wp-content/uploads/2016/11/ASTX_News_2013_1_16_General_Releases.pdf \| https://www.ncbi.nlm.nih.gov/pubmed/22781553	Inhibitor 8297	3.0 nM [IC50]
Rho-associated protein kinase 2 25 Target ID: CHEMBL2973 Sources: http://astx.com/wp-content/uploads/2016/11/ASTX_News_2013_1_16_General_Releases.pdf \| https://www.ncbi.nlm.nih.gov/pubmed/22781553	Inhibitor 8297	4.0 nM [IC50]
Rho-associated protein kinase 1 20 Target ID: CHEMBL3231 Sources: https://www.ncbi.nlm.nih.gov/pubmed/22781553	Inhibitor 8297	6.0 nM [IC50]
Ribosomal protein S6 kinase 1 4 Target ID: CHEMBL4501 Sources: http://astx.com/wp-content/uploads/2016/11/ASTX_News_2013_1_16_General_Releases.pdf \| https://www.ncbi.nlm.nih.gov/pubmed/22781553	Inhibitor 8297	8.0 nM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Advanced solid cancer 28 Sources: https://clinicaltrials.gov/ct2/show/NCT01585701	Primary		Phase I 428	Unknown Approved Use Unknown

C_max

Value	Dose	Analyte	Population
400 nM EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/32616501	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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/32616501	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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/32616501	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 OTHER GOV https://ascopubs.org/doi/abs/10.1200/jco.2014.32.15_suppl.2554	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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/32616501	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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/32616501	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

Value	Dose	Analyte	Population
20000 nM × h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/32616501	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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/32616501	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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/32616501	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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/32616501	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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/32616501	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

T_1/2

Value	Dose	Analyte	Population
40 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/32616501	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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/32616501	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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/32616501	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 OTHER GOV https://ascopubs.org/doi/abs/10.1200/jco.2014.32.15_suppl.2554	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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/32616501	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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/32616501	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

Dose	Population	Adverse 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: https://pubmed.ncbi.nlm.nih.gov/32616501 Page: p.4778	unhealthy, 34–76 n = 6 Health Status: unhealthy Condition: Cancer Age Group: 34–76 Sex: M+F Population Size: 6 Sources: https://pubmed.ncbi.nlm.nih.gov/32616501 Page: p.4778	DLT: Elevated liver enzymes... Dose limiting toxicities: Elevated liver enzymes (16.7%) Sources: https://pubmed.ncbi.nlm.nih.gov/32616501 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: https://pubmed.ncbi.nlm.nih.gov/32616501 Page: p.4778	unhealthy, 34–76 n = 7 Health Status: unhealthy Condition: Cancer Age Group: 34–76 Sex: M+F Population Size: 7 Sources: https://pubmed.ncbi.nlm.nih.gov/32616501 Page: p.4778	DLT: Pneumonitis... Dose limiting toxicities: Pneumonitis (grade 3, 14.3%) Sources: https://pubmed.ncbi.nlm.nih.gov/32616501 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: https://pubmed.ncbi.nlm.nih.gov/32616501 Page: p.4778	unhealthy, 34–76 n = 5 Health Status: unhealthy Condition: Cancer Age Group: 34–76 Sex: M+F Population Size: 5 Sources: https://pubmed.ncbi.nlm.nih.gov/32616501 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: https://pubmed.ncbi.nlm.nih.gov/32616501 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: https://pubmed.ncbi.nlm.nih.gov/32616501 Page: p.4778	unhealthy, 34–76 n = 7 Health Status: unhealthy Condition: Cancer Age Group: 34–76 Sex: M+F Population Size: 7 Sources: https://pubmed.ncbi.nlm.nih.gov/32616501 Page: p.4778	DLT: Maculopapular rash... Dose limiting toxicities: Maculopapular rash (grade 3, 14.3%) Sources: https://pubmed.ncbi.nlm.nih.gov/32616501 Page: p.4778

AEs

AE	Significance	Dose	Population
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: https://pubmed.ncbi.nlm.nih.gov/32616501 Page: p.4778	unhealthy, 34–76 n = 6 Health Status: unhealthy Condition: Cancer Age Group: 34–76 Sex: M+F Population Size: 6 Sources: https://pubmed.ncbi.nlm.nih.gov/32616501 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: https://pubmed.ncbi.nlm.nih.gov/32616501 Page: p.4778	unhealthy, 34–76 n = 7 Health Status: unhealthy Condition: Cancer Age Group: 34–76 Sex: M+F Population Size: 7 Sources: https://pubmed.ncbi.nlm.nih.gov/32616501 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: https://pubmed.ncbi.nlm.nih.gov/32616501 Page: p.4778	unhealthy, 34–76 n = 5 Health Status: unhealthy Condition: Cancer Age Group: 34–76 Sex: M+F Population Size: 5 Sources: https://pubmed.ncbi.nlm.nih.gov/32616501 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: https://pubmed.ncbi.nlm.nih.gov/32616501 Page: p.4778	unhealthy, 34–76 n = 5 Health Status: unhealthy Condition: Cancer Age Group: 34–76 Sex: M+F Population Size: 5 Sources: https://pubmed.ncbi.nlm.nih.gov/32616501 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: https://pubmed.ncbi.nlm.nih.gov/32616501 Page: p.4778	unhealthy, 34–76 n = 5 Health Status: unhealthy Condition: Cancer Age Group: 34–76 Sex: M+F Population Size: 5 Sources: https://pubmed.ncbi.nlm.nih.gov/32616501 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: https://pubmed.ncbi.nlm.nih.gov/32616501 Page: p.4778	unhealthy, 34–76 n = 7 Health Status: unhealthy Condition: Cancer Age Group: 34–76 Sex: M+F Population Size: 7 Sources: https://pubmed.ncbi.nlm.nih.gov/32616501 Page: p.4778

Sourcing

Vendor/Aggregator	ID	URL
1PlusChem LLC	1P008TU9	https://www.1pchem.com/search?query=1P008TU9
A2B Chem	AE11121	http://a2bchem.com/prod/AE11121
AChemBlock	M15888	http://www.achemblock.com/catalogsearch/result/?q=M15888
AK Scientific	2231AH	https://aksci.com/item_detail.php?cat=2231AH
Angene	AGN-PC-0WHA0C	http://www.angenechemical.com/productshow/AGN-PC-0WHA0C.html
ApexBio Technology	B4158	https://www.apexbt.com/catalogsearch/result/?q=B4158
AstaTech	42042	http://astatechinc.com/CPSResult.php?CRNO=42042
Axon MedChem	2166	https://www.axonmedchem.com/product/2166
BLD Pharm	BD285422	http://www.bldpharm.com/search/Search.html?keyword=BD285422
Cayman Chemical	21597	http://www.caymanchem.com/app/template/Product.vm/catalog/21597
Chem Scene	CS-3136	http://www.chemscene.com/goproductList/searchProductList?productObj=CS-3136
ChemShuttle	134417	https://www.chemshuttle.com/catalogsearch/result/?q=134417
Combi-Blocks	QJ-6624	http://www.combi-blocks.com/cgi-bin/find.cgi?QJ-6624
Debye Scientific	DA-35320	https://www.debyesci.com/index.php?id=product&ext[cno]=DA-35320
Excenen	EX-A1797	http://www.excenen.com/searchresultlist.php?id=EX-A1797
Fluorochem	459624	http://www.fluorochem.co.uk/Products/Product?code=459624
KeyOrganics	AS-35164	http://www.keyorganicsinc.com/bionet/catalogsearch/result?q=AS-35164
Lab Network	LN01341916	https://labnetwork.com/frontend-app/p/#!/moleculedetails/LN01341916
Matrix Scientific	153999	http://www.matrixscientific.com/153999.html
MedChem Express	HY-16071	https://www.medchemexpress.com/search.html?q=HY-16071&ft=&fa=&fp=
MolPort	MolPort-035-689-780	https://www.molport.com/shop/molecule-link/MolPort-035-689-780
MolPort	MolPort-042-665-824	https://www.molport.com/shop/molecule-link/MolPort-042-665-824
MolPort	MolPort-042-676-184	https://www.molport.com/shop/molecule-link/MolPort-042-676-184
MuseChem	I000296	https://www.musechem.com/product/I000296.html
Ryan Scientific	101-94135	https://ryansci.com/products?q=101-94135&list_q=&search_type=exact
Ryan Scientific	Rivaroxaban	https://ryansci.com/products?q=Rivaroxaban&list_q=&search_type=exact
Selleck Chemicals	S7563	http://www.selleckchem.com/search.html?searchDTO.searchParam=S7563
ShangHai Biochempartner	BCP08961	http://www.biochempartner.com/search_BCP08961
eMolecules	108760756	https://orderbb.emolecules.com/search/#?query=108760756
eMolecules	275148301	https://orderbb.emolecules.com/search/#?query=275148301
eMolecules	301047945	https://orderbb.emolecules.com/search/#?query=301047945
eMolecules	49435294	https://orderbb.emolecules.com/search/#?query=49435294
eMolecules	49853090	https://orderbb.emolecules.com/search/#?query=49853090
eNovation Chemicals	D501886	https://www.enovationchem.com/Products.asp?SEARCHTEXT=D501886&searchbtn.x=0&searchbtn.y=0
mcule	MCULE-3014373139	https://mcule.com/MCULE-3014373139/
mcule	MCULE-7213160701	https://mcule.com/MCULE-7213160701/

PubMed

Title	Date	PubMed
Role of the anti-glioma drug AT13148 in the inhibition of Notch signaling pathway.	2015 Nov 15	26187072
AT13148, a first-in-class multi-AGC kinase inhibitor, potently inhibits gastric cancer cells both in vitro and in vivo.	2016 Sep 9	26828267

Patents

Sample Use Guides

In Vivo Use Guide

Mice: 50 mg/kg p.o.

Route of Administration: Oral

In Vitro Use Guide

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 UTC 2023` Edited by `admin` on `Sat Dec 16 08:37:14 UTC 2023`
Record UNII	A49037RP1E
Record Status	`Validated (UNII)`
Record Version

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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