UPROSERTIB HYDROCHLORIDE

Investigational

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C18H16Cl2F2N4O2.ClH
Molecular Weight	465.709
Optical Activity	UNSPECIFIED
Defined Stereocenters	1 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

Cl.CN1N=CC(Cl)=C1C2=C(Cl)OC(=C2)C(=O)N[C@H](CN)CC3=CC=C(F)C(F)=C3

InChI

InChIKey=LAPFKCIDRPWAFU-PPHPATTJSA-N

InChI=1S/C18H16Cl2F2N4O2.ClH/c1-26-16(12(19)8-24-26)11-6-15(28-17(11)20)18(27)25-10(7-23)4-9-2-3-13(21)14(22)5-9;/h2-3,5-6,8,10H,4,7,23H2,1H3,(H,25,27);1H/t10-;/m0./s1

HIDE SMILES / InChI

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/24978597 | https://www.ncbi.nlm.nih.gov/pubmed/26932461

Uprosertib is an oral potent Akt inhibitor which acts equally on Akt1, Akt2 and Akt3. The drug is under clinical development in combination with trametinib for the treatment of different cancers, including melanoma, myeloma, breast, endometrial, cervical cancer, etc.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Serine/threonine-protein kinase AKT 31 Target ID: CHEMBL4282 Sources: https://www.ncbi.nlm.nih.gov/pubmed/24978597	Inhibitor 8504	180.0 nM [IC50]
Serine/threonine-protein kinase AKT3 17 Target ID: CHEMBL4816 Sources: https://www.ncbi.nlm.nih.gov/pubmed/24978597	Inhibitor 8504	38.0 nM [IC50]
Serine/threonine-protein kinase AKT2 17 Target ID: CHEMBL2431 Sources: https://www.ncbi.nlm.nih.gov/pubmed/24978597	Inhibitor 8504	328.0 nM [IC50]

Conditions

Condition	Modality	Highest Phase	Product
Melanoma 88 Sources: https://clinicaltrials.gov/ct2/show/NCT01941927	Primary	Phase II 1147	Unknown Approved Use Unknown
Cervical cancer 40 Sources: https://clinicaltrials.gov/ct2/show/NCT01958112	Primary	Phase II 1147	Unknown Approved Use Unknown
Acute myeloid leukemia 3 Sources: https://clinicaltrials.gov/ct2/show/NCT01907815	Primary	Phase II 1147	Unknown Approved Use Unknown
Multiple myeloma 159 Sources: https://clinicaltrials.gov/ct2/show/NCT01989598	Primary	Phase II 1147	Unknown Approved Use Unknown
Triple-negative breast cancer 14 Sources: https://clinicaltrials.gov/ct2/show/NCT01964924	Primary	Phase II 1147	Unknown Approved Use Unknown
Endometrial cancer 44 Sources: https://clinicaltrials.gov/ct2/show/NCT01935973	Primary	Phase II 1147	Unknown Approved Use Unknown
Uveal melanoma 7 Sources: https://clinicaltrials.gov/ct2/show/NCT01979523	Primary	Phase II 1147	Unknown Approved Use Unknown

C_max

Value	Dose	Co-administered	Analyte	Population
409 ng/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/29611022	75 mg 1 times / day steady-state, oral dose: 75 mg route of administration: Oral experiment type: STEADY-STATE co-administered:		UPROSERTIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
94.6 ng/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/29611022	75 mg single, oral dose: 75 mg route of administration: Oral experiment type: SINGLE co-administered:		UPROSERTIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

AUC

Value	Dose	Co-administered	Analyte	Population
6383 ng × h/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/29611022	75 mg 1 times / day steady-state, oral dose: 75 mg route of administration: Oral experiment type: STEADY-STATE co-administered:		UPROSERTIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
1262 ng × h/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/29611022	75 mg single, oral dose: 75 mg route of administration: Oral experiment type: SINGLE co-administered:		UPROSERTIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

T_1/2

Value	Dose	Co-administered	Analyte	Population
63.7 h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/29611022	75 mg 1 times / day steady-state, oral dose: 75 mg route of administration: Oral experiment type: STEADY-STATE co-administered:		UPROSERTIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

Sourcing

Vendor/Aggregator	ID	URL
001 Chemical	DY34176	https://www.001chemical.com/chem/search?q=DY34176
1PlusChem LLC	1P008TXF	https://www.1pchem.com/search?query=1P008TXF
AbovChem LLC	HY-15965A	http://www.abovchem.com/pc/en/product_list.aspx?wd=HY-15965A
ApexBio Technology	B3590	https://www.apexbt.com/catalogsearch/result/?q=B3590
AstaTech	C14076	http://astatechinc.com/CPSResult.php?CRNO=C14076
AstaTech	F20800	http://astatechinc.com/CPSResult.php?CRNO=F20800
BLD Pharm	BD629859	http://www.bldpharm.com/search/Search.html?keyword=BD629859
Cayman Chemical	19904	http://www.caymanchem.com/app/template/Product.vm/catalog/19904
Chem Scene	CS-3087	http://www.chemscene.com/goproductList/searchProductList?productObj=CS-3087
ChemShuttle	140504	https://www.chemshuttle.com/catalogsearch/result/?q=140504
eMolecules	259932074	https://orderbb.emolecules.com/search/#?query=259932074
eMolecules	261291586	https://orderbb.emolecules.com/search/#?query=261291586
eMolecules	301184989	https://orderbb.emolecules.com/search/#?query=301184989
eMolecules	50282260	https://orderbb.emolecules.com/search/#?query=50282260
eMolecules	50283411	https://orderbb.emolecules.com/search/#?query=50283411
Excenen	EX-A1593	http://www.excenen.com/searchresultlist.php?id=EX-A1593
Excenen	EX-A1594	http://www.excenen.com/searchresultlist.php?id=EX-A1594
KeyOrganics	AS-56172	http://www.keyorganicsinc.com/bionet/catalogsearch/result?q=AS-56172
mcule	MCULE-4911475447	https://mcule.com/MCULE-4911475447/
mcule	MCULE-6902422433	https://mcule.com/MCULE-6902422433/
mcule	MCULE-7696692757	https://mcule.com/MCULE-7696692757/
mcule	MCULE-8077537701	https://mcule.com/MCULE-8077537701/
MedChem Express	HY-15965	https://www.medchemexpress.com/search.html?q=HY-15965&ft=&fa=&fp=
Molcore	MC34176	http://www.molcore.com/CatMC34176.html
Molnova	M17123	https://www.molnova.com/en/serch-list.html?keywords=M17123
MolPort	MolPort-044-560-307	https://www.molport.com/shop/molecule-link/MolPort-044-560-307
MolPort	MolPort-044-568-073	https://www.molport.com/shop/molecule-link/MolPort-044-568-073
MuseChem	I009962	https://www.musechem.com/product/I009962.html
Selleck Chemicals	S7492	http://www.selleckchem.com/search.html?searchDTO.searchParam=S7492
ShangHai Biochempartner	BCP28203	http://www.biochempartner.com/search_BCP28203
ShangHai Biochempartner	BCP28204	http://www.biochempartner.com/search_BCP28204
TargetMol	T6849	https://www.targetmol.com/search?keyword=T6849

PubMed

Title	Date	PubMed
Discovery of novel AKT inhibitors with enhanced anti-tumor effects in combination with the MEK inhibitor.	2014	24978597

Patents

Sample Use Guides

In Vivo Use Guide

Melanoma: patients receive oral uprosertib at a dose 25 mg daily. Cervical Cancer: the dose is 50 mg orally once per day.

Route of Administration: Oral

In Vitro Use Guide

Human lung fibroblasts were treated with uprosertib in concentration range from 20 nM to 1.28 uM and analyzed for type I collagen expression. At concentration of 320 nM or higher the drug reduced intracellular level of collagen alpha2(I) polypeptide, while it reduced intracellular alpha olypeptide at concentrations > 640 nM.

Name

Type

Language

UPROSERTIB HYDROCHLORIDE

Common Name

English

2-FURANCARBOXAMIDE, N-((1S)-2-AMINO-1-((3,4-DIFLUOROPHENYL)METHYL)ETHYL)-5-CHLORO-4-(4-CHLORO-1-METHYL-1H-PYRAZOL-5-YL)-, HYDROCHLORIDE (1:1)

Preferred Name

English

Code System Code Type Description

DRUG BANK

DBSALT002113