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Details

Stereochemistry ABSOLUTE
Molecular Formula C25H28Cl2N4O2
Molecular Weight 487.4222
Optical Activity UNSPECIFIED
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of OTS-167

SMILES

CC(=O)c1c[nH]c2ccc(-c3cc(c(c(c3)Cl)O)Cl)nc2c1=N[C@@]4([H])CC[C@@]([H])(CC4)CN(C)C

InChI

InChIKey=DKZYXHCYPUVGAF-JCNLHEQBSA-N
InChI=1S/C25H28Cl2N4O2/c1-14(32)18-12-28-22-9-8-21(16-10-19(26)25(33)20(27)11-16)30-24(22)23(18)29-17-6-4-15(5-7-17)13-31(2)3/h8-12,15,17,33H,4-7,13H2,1-3H3,(H,28,29)/t15-,17-

HIDE SMILES / InChI

Molecular Formula C25H28Cl2N4O2
Molecular Weight 487.4222
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity UNSPECIFIED

OTS-167 is a maternal embryonic leucine zipper kinase (MELK) inhibitor which demonstrated antitumor properties in laboratory tests. It is being developed as an anti-cancer drug. The compound has been shown to suppress the growth of breast, lung, pancreatic and prostate cancer cells that express high levels of the MELK protein. OTS167 reached phase II clinical trials in patients with AML, ALL, advanced MDSs, advanced MPNs, or advanced CML and phase I in patients with breast cancer.

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
Target ID: Q14680|||B7Z6Y0
Gene ID: 9833.0
Gene Symbol: MELK
Target Organism: Homo sapiens (Human)
0.41 nM [IC50]
Conditions
PubMed

PubMed

TitleDatePubMed
Glucuronidation of OTS167 in Humans Is Catalyzed by UDP-Glucuronosyltransferases UGT1A1, UGT1A3, UGT1A8, and UGT1A10.
2015 Jul
OTSSP167 Abrogates Mitotic Checkpoint through Inhibiting Multiple Mitotic Kinases.
2016
Evaluation of human microtubule affinity-regulating kinase 4 inhibitors: fluorescence binding studies, enzyme, and cell assays.
2017 Nov
Patents

Sample Use Guides

In phase I clinical trial on healthy participants OST-167 was given at doses 0.5 mg, 1.0 mg, and 2.0 mg .
Route of Administration: Oral
HeLaM or MCF7 cell lines were treated with 100nM OTS-167 for 2 hours to test the effect of the drug on mitosis.
Substance Class Chemical
Created
by admin
on Sat Jun 26 14:12:26 UTC 2021
Edited
by admin
on Sat Jun 26 14:12:26 UTC 2021
Record UNII
VY778IXU5T
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
OTS-167
Common Name English
ETHANONE, 1-(6-(3,5-DICHLORO-4-HYDROXYPHENYL)-4-((TRANS-4-((DIMETHYLAMINO)METHYL)CYCLOHEXYL)AMINO)-1,5-NAPHTHYRIDIN-3-YL)-
Systematic Name English
OTS167
Code English
MELK INHIBITOR OTS167
Common Name English
OTSSP-167
Code English
OTSSP167
Code English
Classification Tree Code System Code
NCI_THESAURUS C61074
Created by admin on Sat Jun 26 14:12:26 UTC 2021 , Edited by admin on Sat Jun 26 14:12:26 UTC 2021
Code System Code Type Description
CAS
1431697-89-0
Created by admin on Sat Jun 26 14:12:26 UTC 2021 , Edited by admin on Sat Jun 26 14:12:26 UTC 2021
PRIMARY
EPA CompTox
1431697-89-0
Created by admin on Sat Jun 26 14:12:26 UTC 2021 , Edited by admin on Sat Jun 26 14:12:26 UTC 2021
PRIMARY
NCI_THESAURUS
C111569
Created by admin on Sat Jun 26 14:12:26 UTC 2021 , Edited by admin on Sat Jun 26 14:12:26 UTC 2021
PRIMARY
MANUFACTURER PRODUCT INFORMATION
OTS-167
Created by admin on Sat Jun 26 14:12:26 UTC 2021 , Edited by admin on Sat Jun 26 14:12:26 UTC 2021
PRIMARY Description: Maternal embryonic leucine zipper kinase (MELK) is a serine/threonine kinase that regulates signaling central to cell cycling, stem cell renewal, apoptosis, and other cellular processes. MELK is overexpressed in some forms of cancer, particularly those with aggressive undifferentiated tumors. OTSSP167 is a potent inhibitor of MELK (IC50 = 0.41 nM). It suppresses the growth of diverse cancer cell lines at low nanomolar concentrations.5 It also blocks the phosphorylation of MELK-specific substrates and reduces the ability of MCF-7 breast cancer cells to invade and form spheroids in Matrigel.5 OTSSP167 is also effective in vivo when delivered either orally or intravenously, suppressing the growth of xenograft tumors in mice.
FDA UNII
VY778IXU5T
Created by admin on Sat Jun 26 14:12:26 UTC 2021 , Edited by admin on Sat Jun 26 14:12:26 UTC 2021
PRIMARY
Related Record Type Details
SALT/SOLVATE -> PARENT
TARGET -> INHIBITOR
Related Record Type Details
ACTIVE MOIETY
OTSSP167 is an inhibitor of maternal embryonic leucine zipper kinase (MELK) with IC50 value of 0.41nM. MELK is a member of the AMPK serine/threonine kinase family and is involved in the mammalian embryonic development. It plays roles in cancer cell growth and formation or maintenance of cancer stem cells. OTSSP167 is a small-molecule inhibitor and can inhibit MELKs activity effectively and selectively. OTSSP167 inhibits cell proliferation of a variety of cancer cell lines including A549, T47D, DU4475 and 22Rv1. The IC50 values are 6.7nM, 4.3nM, 2.3nM and 6nM, respectively. In mice bearing MDA-MB-231 xenograft, administration of OTSSP167 inhibits 70% tumor growth at dose of 20 mg/kg. Besides that, OTSSP167 is also found to have effects on PSMA1 and DBNL which are the novel substrates of MELK. It inhibits the phosphorylation of PSMA1 and DBNL causes the subsequent suppression of mammosphere formation.