U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

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 of PHA-793887

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
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

Unknown
139594
Targets

Targets

Primary TargetPharmacologyConditionPotency
Inhibitor
8297
 5.0 nM [IC50]
Inhibitor
8297
 8.0 nM [IC50]
Inhibitor
8297
 8.0 nM [IC50]
Inhibitor
8297
 10.0 nM [IC50]
Inhibitor
8297
 60.0 nM [IC50]
Inhibitor
8297
 62.0 nM [IC50]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Phase I
428
Unknown

Approved Use

Unknown
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
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

AUC

ValueDoseCo-administeredAnalytePopulation
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
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
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

Sourcing

Vendor/AggregatorIDURL
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

PubMed

TitleDatePubMed
Optimization of 6,6-dimethyl pyrrolo[3,4-c]pyrazoles: Identification of PHA-793887, a potent CDK inhibitor suitable for intravenous dosing.
2010 Mar 1
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
Patents

Patents

20070004705
3

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 UTC 2023
Edited
by admin
on Sat Dec 16 10:31:19 UTC 2023
Record UNII
MKS45S912B
Record Status Validated (UNII)
Record Version
  • Download
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
Created by admin on Sat Dec 16 10:31:19 UTC 2023 , Edited by admin on Sat Dec 16 10:31:19 UTC 2023
PRIMARY
EPA CompTox
DTXSID50222134
Created by admin on Sat Dec 16 10:31:19 UTC 2023 , Edited by admin on Sat Dec 16 10:31:19 UTC 2023
PRIMARY
FDA UNII
MKS45S912B
Created by admin on Sat Dec 16 10:31:19 UTC 2023 , Edited by admin on Sat Dec 16 10:31:19 UTC 2023
PRIMARY
ChEMBL
CHEMBL1230607
Created by admin on Sat Dec 16 10:31:19 UTC 2023 , Edited by admin on Sat Dec 16 10:31:19 UTC 2023
PRIMARY
CAS
718630-59-2
Created by admin on Sat Dec 16 10:31:19 UTC 2023 , Edited by admin on Sat Dec 16 10:31:19 UTC 2023
PRIMARY
DRUG BANK
DB12686
Created by admin on Sat Dec 16 10:31:19 UTC 2023 , Edited by admin on Sat Dec 16 10:31:19 UTC 2023
PRIMARY
PUBCHEM
46191454
Created by admin on Sat Dec 16 10:31:19 UTC 2023 , Edited by admin on Sat Dec 16 10:31:19 UTC 2023
PRIMARY
Related Record Type Details
Structure of PHA-793887 HYDROCHLORIDE
PARENT -> SALT/SOLVATE
CYCLIN-DEPENDENT-LIKE KINASE 5
TARGET -> INHIBITOR
IC50
CYCLIN D1-CDK4 COMPLEX
TARGET -> INHIBITOR
IC50
GLYCOGEN SYNTHASE KINASE-3 BETA
OFF-TARGET->INHIBITOR
IC50
CYCLIN-DEPENDENT KINASE 2
TARGET -> INHIBITOR
IC50
CYCLIN-DEPENDENT KINASE 9
TARGET -> INHIBITOR
Cyclin T1-CDK9 COMPLEX
TARGET -> INHIBITOR
IC50
CYCLIN E1-CDK2 COMPLEX
TARGET -> INHIBITOR
IC50
CYCLIN-DEPENDENT KINASE 1
TARGET -> INHIBITOR
IC50
CYCLIN-DEPENDENT KINASE 4
TARGET -> INHIBITOR
IC50
Related Record Type Details
CYCLIN-DEPENDENT KINASE 7
ACTIVE MOIETY
IC50
Structure of PHA-793887
ACTIVE MOIETY
NIH
NCATS
PRIVACY ACT
ACCESSIBILITY
DISCLAIMER
HHS VULNERABILITY DISCLOSURE
For language access assistance, contact the NCATS Public Information Officer
National Center for Advancing Translational Sciences (NCATS),
6701 Democracy Boulevard, Bethesda MD 20892-4874 • 301-594-8966