CYCLIN-DEPENDENT KINASE 7

Investigational

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
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	20153204
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	Protein Created by `admin` on `Sat Dec 16 11:29:14 UTC 2023` Edited by `admin` on `Sat Dec 16 11:29:14 UTC 2023`
Protein Sub Type
Sequence Origin	HUMAN
Sequence Type	COMPLETE
Record UNII	QVI13FG2SW
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

CYCLIN-DEPENDENT KINASE 7

Common Name

English

TFIIH BASAL TRANSCRIPTION FACTOR COMPLEX KINASE SUBUNIT

Common Name

English

CDK-ACTIVATING KINASE 1

Common Name

English

SERINE/THREONINE-PROTEIN KINASE 1

Common Name

English

CDK-7

Common Name

English

STK1

Common Name

English

MO15

Common Name

English

P39 MO15

Common Name

English

CDKN7

Common Name

English

39 KDA PROTEIN KINASE

Common Name

English

CAK1

Common Name

English

CDK7

Common Name

English

CELL DIVISION PROTEIN KINASE 7

Common Name

English

CAK

Common Name

English

Code System Code Type Description

FDA UNII

QVI13FG2SW

Created by admin on Sat Dec 16 11:29:15 UTC 2023 , Edited by admin on Sat Dec 16 11:29:15 UTC 2023

PRIMARY

PHAROS

P50613

Created by admin on Sat Dec 16 11:29:15 UTC 2023 , Edited by admin on Sat Dec 16 11:29:15 UTC 2023

PRIMARY

UNIPROT

P50613

Created by admin on Sat Dec 16 11:29:15 UTC 2023 , Edited by admin on Sat Dec 16 11:29:15 UTC 2023

PRIMARY

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Name	Property Type	Amount	Referenced Substance	Defining	Parameters	References
MOL_WEIGHT	CHEMICAL

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

Originator

Approval Year

Targets

Conditions

Approved Use

Cmax

AUC

T1/2

Sourcing

PubMed

Patents

Sample Use Guides

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

C_max

T_1/2