PHA-793887

Investigational

Details

Stereochemistry	ACHIRAL
Molecular Formula	C19H31N5O2
Molecular Weight	361.4817
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CC(C)CC(=O)NC1=NNC2=C1CN(C(=O)C3CCN(C)CC3)C2(C)C

InChI

InChIKey=HUXYBQXJVXOMKX-UHFFFAOYSA-N

InChI=1S/C19H31N5O2/c1-12(2)10-15(25)20-17-14-11-24(19(3,4)16(14)21-22-17)18(26)13-6-8-23(5)9-7-13/h12-13H,6-11H2,1-5H3,(H2,20,21,22,25)

HIDE SMILES / InChI

Molecular Formula	C19H31N5O2
Molecular Weight	361.4817
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/20167248 | https://www.ncbi.nlm.nih.gov/pubmed/20153204
Curator's Comment: Description was created based on several sources, including

PHA-793887 is an inhibitor of multiple cyclin dependent kinases (CDK) with activity against CDK2, CDK1 and CDK4. PHA-793887 was cytotoxic for leukemic cell lines in vitro, with IC(50) ranging from 0.3 to 7 uM. In colony assays PHA-793887 showed very high activity against leukemia cell lines, with an IC(50) <0.1 uM indicating that it has efficient and prolonged antiproliferative activity. PHA-793887 induced cell-cycle arrest, inhibited Rb and nucleophosmin phosphorylation. PHA-793887 has promising therapeutic activity against acute leukemias in vitro and in vivo.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Cyclin-dependent kinase 5/CDK5 activator 1 8 Target ID: CHEMBL1907600 Sources: https://www.ncbi.nlm.nih.gov/pubmed/20153204	Inhibitor 8297	5.0 nM [IC50]
Cyclin-dependent kinase 2/cyclin A 8 Target ID: CHEMBL2094128 Sources: https://www.ncbi.nlm.nih.gov/pubmed/20153204	Inhibitor 8297	8.0 nM [IC50]
Cyclin-dependent kinase 2/cyclin E1 4 Target ID: CHEMBL1907605 Sources: https://www.ncbi.nlm.nih.gov/pubmed/20153204	Inhibitor 8297	8.0 nM [IC50]
Cyclin-dependent kinase 7/ cyclin H 7 Target ID: CHEMBL2111288 Sources: https://www.ncbi.nlm.nih.gov/pubmed/20153204	Inhibitor 8297	10.0 nM [IC50]
Cyclin-dependent kinase 1/cyclin B1 6 Target ID: CHEMBL1907602 Sources: https://www.ncbi.nlm.nih.gov/pubmed/20153204	Inhibitor 8297	60.0 nM [IC50]
Cyclin-dependent kinase 4/cyclin D1 11 Target ID: CHEMBL1907601 Sources: https://www.ncbi.nlm.nih.gov/pubmed/20153204	Inhibitor 8297	62.0 nM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Solid tumors 145 Sources: https://clinicaltrials.gov/ct2/show/NCT00996255	Primary		Phase I 428	Unknown Approved Use Unknown

C_max

Value	Dose	Co-administered	Analyte	Population
3.607 μM EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/21368575	44 mg/m² 1 times / week multiple, intravenous dose: 44 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered:		PHA-793887 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
5.807 μM EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/21368575	66 mg/m² 1 times / week multiple, intravenous dose: 66 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered:		PHA-793887 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

AUC

Value	Dose	Co-administered	Analyte	Population
10.148 μM × h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/21368575	44 mg/m² 1 times / week multiple, intravenous dose: 44 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered:		PHA-793887 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
13.072 μM × h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/21368575	66 mg/m² 1 times / week multiple, intravenous dose: 66 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered:		PHA-793887 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

T_1/2

Value	Dose	Co-administered	Analyte	Population
9.177 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/21368575	44 mg/m² 1 times / week multiple, intravenous dose: 44 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered:		PHA-793887 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
7.247 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/21368575	66 mg/m² 1 times / week multiple, intravenous dose: 66 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered:		PHA-793887 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

Sourcing

Vendor/Aggregator	ID	URL
001 Chemical	DY443030	https://www.001chemical.com/chem/search?q=DY443030
1PlusChem LLC	1P005FT7	https://www.1pchem.com/search?query=1P005FT7
A2B Chem	AC52971	http://a2bchem.com/prod/AC52971
AK Scientific	X7380	https://aksci.com/item_detail.php?cat=X7380
AOBIOUS INC	AOB87190	http://aobious.com/aobious/search?search_query=AOB87190
Aceschem	ACS019892	https://www.aceschem.com/catalog/search.do?q=ACS019892
Angene	AGN-PC-07PXPC	http://www.angenechemical.com/productshow/AGN-PC-07PXPC.html
ApexBio Technology	A5459	https://www.apexbt.com/catalogsearch/result/?q=A5459
AstaTech	C76289	http://astatechinc.com/CPSResult.php?CRNO=C76289
BLD Pharm	BD559223	http://www.bldpharm.com/search/Search.html?keyword=BD559223
Capot Chemical	34012	https://www.capotchem.com/search.do?q=34012
Cayman Chemical	18388	http://www.caymanchem.com/app/template/Product.vm/catalog/18388
Chem Scene	CS-0020	http://www.chemscene.com/goproductList/searchProductList?productObj=CS-0020
ChemShuttle	113090	https://www.chemshuttle.com/catalogsearch/result/?q=113090
Debye Scientific	DB-074487	https://www.debyesci.com/index.php?id=product&ext[cno]=DB-074487
Excenen	EX-A2134	http://www.excenen.com/searchresultlist.php?id=EX-A2134
Hairui	HR33043	http://www.hairuichem.com/en/product/search.do?q=HR33043
KeyOrganics	AS-19371	http://www.keyorganicsinc.com/bionet/catalogsearch/result?q=AS-19371
Lab Network	LN01306104	https://labnetwork.com/frontend-app/p/#!/moleculedetails/LN01306104
Lab Seeker	SC-96644	http://www.labseeker.com/search.php?keywords=SC-96644&category=0
LabSeeker	SC-96644	http://www.labseeker.com/search.php?keywords=SC-96644&category=0
Matrix Scientific	147638	http://www.matrixscientific.com/147638.html
MedChem Express	HY-11001	https://www.medchemexpress.com/search.html?q=HY-11001&ft=&fa=&fp=
MolPort	MolPort-009-679-503	https://www.molport.com/shop/molecule-link/MolPort-009-679-503
Molcore	MC443030	http://www.molcore.com/CatMC443030.html
Molnova	M15748	https://www.molnova.com/en/serch-list.html?keywords=M15748
MuseChem	I008740	https://www.musechem.com/product/I008740.html
Ryan Scientific	P7C3	https://ryansci.com/products?q=P7C3&list_q=&search_type=exact
ShangHai Biochempartner	BCP02036	http://www.biochempartner.com/search_BCP02036
Toronto Research Chemicals	M265448	https://www.trc-canada.com/product-detail/?CatNum=M265448
Toronto Research Chemicals	P294480	https://www.trc-canada.com/product-detail/?CatNum=P294480
eMolecules	32176634	https://orderbb.emolecules.com/search/#?query=32176634
eMolecules	43473287	https://orderbb.emolecules.com/search/#?query=43473287
eNovation Chemicals	D395244	https://www.enovationchem.com/Products.asp?SEARCHTEXT=D395244&searchbtn.x=0&searchbtn.y=0
mcule	MCULE-7233148866	https://mcule.com/MCULE-7233148866/

PubMed

Title	Date	PubMed
Transcriptional analysis of an E2F gene signature as a biomarker of activity of the cyclin-dependent kinase inhibitor PHA-793887 in tumor and skin biopsies from a phase I clinical study.	2010 May	20423997

Patents

Sample Use Guides

In Vivo Use Guide

Mice: PHA-793887 was administered at 20 mg/kg intravenous (IV) once a day, continuously for 10 days (from day 9 to day 18) in HL60 model and with a two 5-day cycles (from day 9 to day 13 and from day 17 to day 21) in K562-bearing mice.

Route of Administration: Oral

In Vitro Use Guide

PHA-793887 was cytotoxic for leukemic cell lines in vitro, with IC(50) ranging from 0.3 to 7 uM (mean: 2.9 uM). in colony assays PHA-793887 showed very high activity against leukemia cell lines, with an IC(50) <0.1 uM (mean: 0.08 uM). PHA-793887 induced cell-cycle arrest, inhibited Rb and nucleophosmin phosphorylation, and modulated cyclin E and cdc6 expression at low doses (0.2-1 uM) and induced apoptosis at the highest dose (5 uM).

Substance Class	Chemical Created by `admin` on `Sat Dec 16 10:31:19 GMT 2023` Edited by `admin` on `Sat Dec 16 10:31:19 GMT 2023`
Record UNII	MKS45S912B
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

PHA-793887

Common Name

English

N-(6,6-DIMETHYL-5-(1-METHYLPIPERIDINE-4-CARBONYL)-1,4,5,6-TETRAHYDROPYRROLO(3,4-C)PYRAZOL-3-YL)-3-METHYLBUTANAMIDE

Systematic Name

English

BUTANAMIDE, 3-METHYL-N-(1,4,5,6-TETRAHYDRO-6,6-DIMETHYL-5-((1-METHYL-4-PIPERIDINYL)CARBONYL)PYRROLO(3,4-C)PYRAZOL-3-YL)-

Systematic Name

English

Code System Code Type Description

SMS_ID

300000041367