CBL-0137 FREE BASE

Investigational

Details

Stereochemistry	ACHIRAL
Molecular Formula	C21H24N2O2
Molecular Weight	336.4275
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CC(C)NCCN1C2=CC=C(C=C2C3=C1C=CC(=C3)C(C)=O)C(C)=O

InChI

InChIKey=JKCSODVERGVDLT-UHFFFAOYSA-N

InChI=1S/C21H24N2O2/c1-13(2)22-9-10-23-20-7-5-16(14(3)24)11-18(20)19-12-17(15(4)25)6-8-21(19)23/h5-8,11-13,22H,9-10H2,1-4H3

HIDE SMILES / InChI

Molecular Formula	C21H24N2O2
Molecular Weight	336.4275
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Description
Sources: http://www.cbiolabs.com/cbl0137 | https://www.ncbi.nlm.nih.gov/pubmed/25402820

CBL0137 (also known as Curaxin CBL0137) is a metabolically stable curaxin and belongs to the class of small molecules with anti-cancer activity. CBL0137 is in Phase I clinical trials to treat hematological malignancies and solid tumors. CBL0137 binds to Facilitates Chromatin Transcription (FACT) and sequesters the FACT complex on chromatin, which inhibits its activity. This prevents transcription of certain genes involved in cancer-associated signaling pathways; it specifically inhibits the transcription of both NF-kappa β and heat shock transcription factor 1 (HSF1) and simultaneously activates p53. In addition, CBL0137 was investigated in vitro and in models mice for pancreatic ductal adenocarcinoma (PDA) and the obtained data suggested testing of CBL0137 efficacy in Phase II trial in PDA patients alone and in combination with gemcitabine.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
FACT complex 2 Target ID: FACT complex Sources: https://www.ncbi.nlm.nih.gov/pubmed/21832239	Inhibitor 8297

Conditions

Condition	Modality	Targets	Highest Phase	Product
Hematologic malignancies 19 Sources: https://clinicaltrials.gov/ct2/show/NCT02931110	Primary		Phase I 428	Unknown Approved Use Unknown
Pancreatic ductal adenocarcinoma 14 Sources: https://www.ncbi.nlm.nih.gov/pubmed/25402820	Primary		Preclinical	Unknown Approved Use Unknown

Overview

CYP3A4	CYP2C9	CYP2D6	hERG

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
	Multidrug Transporters 2

Drug as victim

Target	Modality	Activity	Metabolite	Clinical evidence
Multidrug Transporters 2	substrate 3367 Sources: http://www.cbiolabs.org/wp-content/uploads/2016/05/ECCOposter9-2013.pdf	no

Sourcing

Vendor/Aggregator	ID	URL
1PlusChem LLC	1P000Q44	https://www.1pchem.com/search?query=1P000Q44
1PlusChem LLC	1P01EBJ7	https://www.1pchem.com/search?query=1P01EBJ7
AChemBlock	Q70179	http://www.achemblock.com/catalogsearch/result/?q=Q70179
ApexBio Technology	C3171	https://www.apexbt.com/catalogsearch/result/?q=C3171
ApexBio Technology	C3192	https://www.apexbt.com/catalogsearch/result/?q=C3192
Cayman Chemical	19110	http://www.caymanchem.com/app/template/Product.vm/catalog/19110
Cayman Chemical	19373	http://www.caymanchem.com/app/template/Product.vm/catalog/19373
Chem Scene	CS-0033711	http://www.chemscene.com/goproductList/searchProductList?productObj=CS-0033711
ChemShuttle	140440	https://www.chemshuttle.com/catalogsearch/result/?q=140440
MedChem Express	HY-18935A	https://www.medchemexpress.com/search.html?q=HY-18935A&ft=&fa=&fp=
MolPort	MolPort-027-946-934	https://www.molport.com/shop/molecule-link/MolPort-027-946-934
MolPort	MolPort-044-561-572	https://www.molport.com/shop/molecule-link/MolPort-044-561-572
Molnova	M10708	https://www.molnova.com/en/serch-list.html?keywords=M10708
Molnova	M17184	https://www.molnova.com/en/serch-list.html?keywords=M17184
MuseChem	I006313	https://www.musechem.com/product/I006313.html
ShangHai Biochempartner	BCP29139	http://www.biochempartner.com/search_BCP29139
TargetMol	T4361	https://www.targetmol.com/search?keyword=T4361
Toronto Research Chemicals	C227210	https://www.trc-canada.com/product-detail/?CatNum=C227210
eMolecules	44846180	https://orderbb.emolecules.com/search/#?query=44846180
eMolecules	75542314	https://orderbb.emolecules.com/search/#?query=75542314
eNovation Chemicals	D621173	https://www.enovationchem.com/Products.asp?SEARCHTEXT=D621173&searchbtn.x=0&searchbtn.y=0
mcule	MCULE-4953039479	https://mcule.com/MCULE-4953039479/
mcule	MCULE-7361782774	https://mcule.com/MCULE-7361782774/

PubMed

Title	Date	PubMed
Curaxins: anticancer compounds that simultaneously suppress NF-κB and activate p53 by targeting FACT.	2011 Aug 10	21832239
Curaxin CBL0137 eradicates drug resistant cancer stem cells and potentiates efficacy of gemcitabine in preclinical models of pancreatic cancer.	2014 Nov 30	25402820

Sample Use Guides

In Vivo Use Guide

Dose Level 1: 120mg/m2, IV; dose Level 2: 150mg/m2, IV; dose Level 3: 180mg/m2, IV; dose Level 4: 240mg/m2, IV; dose Level 5: 20mg/m2, IV; dose Level 6: 400mg/m2, IV. All dose are on Days 1 and 8 of every 22 day cycle. Number of Cycles: 2 or until progression or unacceptable toxicity develops.

Route of Administration: Intravenous

In Vitro Use Guide

To test the effect of CBL0137 on gemcitabine-sensitive and -resistant Pancreatic ductal adenocarcinoma (PDA) cells, MiaPaCa-2 and PANC-1 human PDA cell lines were used, which are gemcitabine-sensitive and resistant, respectively. Both cell lines were sensitive to CBL0137 in 72h viability assays. Importantly, while treatment with CBL0137 (range of concentration is 0-6 uM) led to complete absence of living cells at concentrations above 2.5 μM, gemcitabine treatment, which as reported was more effective against MiaPaCa-2 than PANC-1 cells, resulted in growth arrest rather than cell death since no reduction in the number of living cells were observed with dose escalation.

Substance Class	Chemical Created by `admin` on `Sat Dec 16 09:54:19 GMT 2023` Edited by `admin` on `Sat Dec 16 09:54:19 GMT 2023`
Record UNII	8XKR07H9ER
Record Status	`Validated (UNII)`
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CBL-0137 FREE BASE

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8XKR07H9ER