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Details

Stereochemistry ACHIRAL
Molecular Formula C23H25ClFN7O
Molecular Weight 469.9431
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of GANDOTINIB

SMILES

Cc1cc(=Nc2cc(CN3CCOCC3)c4nc(C)c(Cc5ccc(cc5F)Cl)n4n2)[nH][nH]1

InChI

InChIKey=SQSZANZGUXWJEA-UHFFFAOYSA-N
InChI=1S/C23H25ClFN7O/c1-14-9-21(29-28-14)27-22-11-17(13-31-5-7-33-8-6-31)23-26-15(2)20(32(23)30-22)10-16-3-4-18(24)12-19(16)25/h3-4,9,11-12H,5-8,10,13H2,1-2H3,(H2,27,28,29,30)

HIDE SMILES / InChI

Molecular Formula C23H25ClFN7O
Molecular Weight 469.9431
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: http://www.pharmacodia.com/yaodu/html/v1/chemicals/6eab78f10219a83895b2e2d71dc0656e.html | https://www.ncbi.nlm.nih.gov/pubmed/23317159 | https://www.ncbi.nlm.nih.gov/pubmed/22227528

An orally bioavailable imidazopyridazine and inhibitor of Janus kinase 2 mutant V617F (JAK2V617F), with potential antineoplastic activity. Upon oral administration, gandotinib selectively and competitively inhibits the activation of JAK2V617F, which may result in the inhibition of the JAK-STAT signaling pathway and the induction of apoptosis in JAK2V617F-expressing tumor cells. Gandotinib is in phase II clinical trials by Lilly for the treatment of myeloproliferative disorders.

Originator

Curator's Comment:: # Eli Lilly

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
0.055 µM [IC50]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Curative
Unknown

Approved Use

Unknown
Primary
Unknown

Approved Use

Unknown
Sourcing

Sourcing

Vendor/AggregatorIDURL
PubMed

PubMed

TitleDatePubMed
Patents

Sample Use Guides

120 mg administered once daily for 6 cycles (168 days).
Route of Administration: Oral
LY2784544 effectively inhibited JAK2V617F-driven signaling and cell proliferation in Ba/F3 cells (IC50=20 and 55 nM, respectively). In comparison, LY2784544 was much less potent at inhibiting interleukin-3-stimulated wild-type JAK2-mediated signaling and cell proliferation (IC50=1183 and 1309 nM, respectively).
Substance Class Chemical
Created
by admin
on Sat Jun 26 03:10:12 UTC 2021
Edited
by admin
on Sat Jun 26 03:10:12 UTC 2021
Record UNII
ANC71R916O
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
GANDOTINIB
INN   USAN   WHO-DD  
INN   USAN  
Official Name English
3-(4-CHLORO-2-FLUOROBENZYL)-2-METHYL-N-(5-METHYL-1H-PYRAZOL-3-YL)-8- (MORPHOLINOMETHYL)IMIDAZO(1,2-B)PYRIDAZIN-6-AMINE
Systematic Name English
IMIDAZO(1,2-B)PYRIDAZIN-6-AMINE, 3-((4-CHLORO-2-FLUOROPHENYL)METHYL)-2-METHYL-N-(5- METHYL-1H-PYRAZOL-3-YL)-8-(4-MORPHOLINYLMETHYL)-
Common Name English
GANDOTINIB [INN]
Common Name English
LY2784544
Code English
GANDOTINIB [USAN]
Common Name English
3-((4-CHLORO-2-FLUOROPHENYL)METHYL)-2-METHYL-N-(5-METHYL-1H-PYRAZOL-3-YL)-8- (MORPHOLIN-4-YLMETHYL)IMIDAZO(1,2-B)PYRIDAZIN-6-AMINE
Systematic Name English
LY-2784544
Code English
GANDOTINIB [WHO-DD]
Common Name English
Classification Tree Code System Code
FDA ORPHAN DRUG 334211
Created by admin on Sat Jun 26 03:10:12 UTC 2021 , Edited by admin on Sat Jun 26 03:10:12 UTC 2021
NCI_THESAURUS C1967
Created by admin on Sat Jun 26 03:10:12 UTC 2021 , Edited by admin on Sat Jun 26 03:10:12 UTC 2021
NCI_THESAURUS C129825
Created by admin on Sat Jun 26 03:10:12 UTC 2021 , Edited by admin on Sat Jun 26 03:10:12 UTC 2021
Code System Code Type Description
ChEMBL
CHEMBL2107823
Created by admin on Sat Jun 26 03:10:12 UTC 2021 , Edited by admin on Sat Jun 26 03:10:12 UTC 2021
PRIMARY
EVMPD
SUB128915
Created by admin on Sat Jun 26 03:10:12 UTC 2021 , Edited by admin on Sat Jun 26 03:10:12 UTC 2021
PRIMARY
FDA UNII
ANC71R916O
Created by admin on Sat Jun 26 03:10:12 UTC 2021 , Edited by admin on Sat Jun 26 03:10:12 UTC 2021
PRIMARY
WIKIPEDIA
Gandotinib
Created by admin on Sat Jun 26 03:10:12 UTC 2021 , Edited by admin on Sat Jun 26 03:10:12 UTC 2021
PRIMARY
DRUG BANK
DB13040
Created by admin on Sat Jun 26 03:10:12 UTC 2021 , Edited by admin on Sat Jun 26 03:10:12 UTC 2021
PRIMARY
NCI_THESAURUS
C116857
Created by admin on Sat Jun 26 03:10:12 UTC 2021 , Edited by admin on Sat Jun 26 03:10:12 UTC 2021
PRIMARY
INN
9695
Created by admin on Sat Jun 26 03:10:12 UTC 2021 , Edited by admin on Sat Jun 26 03:10:12 UTC 2021
PRIMARY
EPA CompTox
1229236-86-5
Created by admin on Sat Jun 26 03:10:12 UTC 2021 , Edited by admin on Sat Jun 26 03:10:12 UTC 2021
PRIMARY
PUBCHEM
46213929
Created by admin on Sat Jun 26 03:10:12 UTC 2021 , Edited by admin on Sat Jun 26 03:10:12 UTC 2021
PRIMARY
CAS
1229236-86-5
Created by admin on Sat Jun 26 03:10:12 UTC 2021 , Edited by admin on Sat Jun 26 03:10:12 UTC 2021
PRIMARY
Related Record Type Details
TARGET -> INHIBITOR
KI (nM) as determined in a kinetic ATP-based mechanism of action assay;
COMPETITIVE INHIBITOR
Ki
TARGET->WEAK INHIBITOR
COMPETITIVE INHIBITOR
IC50
TARGET -> INHIBITOR
Biochemical measurement of JAK inhibition; Used JAK LanthaScreen Kinase assay.
COMPETITIVE INHIBITOR
IC50
TARGET -> INHIBITOR
Cellular assay; EPO TF-1 JAK2; Used Cellomics detection format.
COMPETITIVE INHIBITOR
IC50
TARGET -> INHIBITOR
TARGET->WEAK INHIBITOR
cellular assay;IL-2 NK-92 JAK3/JAK1; Used Cellomics detection format.
COMPETITIVE INHIBITOR
IC50
TARGET -> INHIBITOR
Cell proliferation assay
COMPETITIVE INHIBITOR
IC50
TARGET -> INHIBITOR
pSTAT5 AlphaScreen assay
COMPETITIVE INHIBITOR
IC50
Related Record Type Details
ACTIVE MOIETY