RO-5-3335

Details

Stereochemistry	ACHIRAL
Molecular Formula	C13H10ClN3O
Molecular Weight	259.691
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

ClC1=CC2=C(NC(=O)CN=C2C3=CC=CN3)C=C1

InChI

InChIKey=XWNMORIHKRROGW-UHFFFAOYSA-N

InChI=1S/C13H10ClN3O/c14-8-3-4-10-9(6-8)13(11-2-1-5-15-11)16-7-12(18)17-10/h1-6,15H,7H2,(H,17,18)

HIDE SMILES / InChI

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/1763331 | https://www.ncbi.nlm.nih.gov/pubmed/1397654 | https://www.ncbi.nlm.nih.gov/pubmed/22912405 | http://adisinsight.springer.com/drugs/800002484

Ro 5-3335, 7-chloro-5-(2-pyrryl)-3H-1,4-benzo-diazepin-2-(H)-one, is a benzodiazepine compound. Originally Ro 5-3335 was shown to inhibit gene expression controlled by the human immunodeficiency virus-1 (HIV-1) LTR promoter. The inhibition was specific for the viral transcriptional transactivator Tat. The compound did not inhibit the basal activity of the HIV-1 LTR or the activity of promoters not responsive to Tat. In addition Ro 5-3335 was able to interact with RUNX1 and CBFβ directly, repress RUNX1/CBFB-dependent transactivation in reporter assays, and repress runx1-dependent hematopoiesis in zebrafish embryos. Ro5-3335 preferentially killed human CBF leukemia cell lines, rescued preleukemic phenotype in a RUNX1-ETO transgenic zebrafish, and reduced leukemia burden in a mouse CBFB-MYH11 leukemia model.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Human immunodeficiency virus type 1 Tat protein 1 Target ID: CHEMBL4011 Sources: https://www.ncbi.nlm.nih.gov/pubmed/1763331 \| https://www.ncbi.nlm.nih.gov/pubmed/1397654	Inhibitor 8504
Runt-related transcription factor 1/Core-binding factor subunit beta 1 Target ID: CHEMBL2093862 Sources: https://www.ncbi.nlm.nih.gov/pubmed/22912405	Inhibitor 8504

Conditions

Condition	Modality	Highest Phase	Product
HIV-1 infection 156 Sources: https://www.ncbi.nlm.nih.gov/pubmed/1763331 https://www.ncbi.nlm.nih.gov/pubmed/1397654	Primary	Preclinical	Unknown Approved Use Unknown
Leukemia 72 Sources: https://www.ncbi.nlm.nih.gov/pubmed/22912405	Primary	Preclinical	Unknown Approved Use Unknown
Septic shock 21 Sources: https://www.ncbi.nlm.nih.gov/pubmed/27573239	Primary	Preclinical	Unknown Approved Use Unknown

PubMed

Title	Date	PubMed
Inhibitors of human immunodeficiency virus type 1 reverse transcriptase target distinct phases of early reverse transcription.	2001-04	11238836
A second target for the peptoid Tat/transactivation response element inhibitor CGP64222: inhibition of human immunodeficiency virus replication by blocking CXC-chemokine receptor 4-mediated virus entry.	2000-01	10617686
S-adenosylhomocysteine hydrolase inhibitors interfere with the replication of human immunodeficiency virus type 1 through inhibition of the LTR transactivation.	1997-12	9396786
Discovery of selective, small-molecule inhibitors of RNA complexes--I. The Tat protein/TAR RNA complexes required for HIV-1 transcription.	1997-06	9222511
2-Glycineamide-5-chlorophenyl 2-pyrryl ketone, a non-benzodiazepin Tat antagonist, is effective against acute and chronic HIV-1 infections in vitro.	1996-10	8891164
Compounds that target novel cellular components involved in HIV-1 transcription.	1995-11	8612198
The human immunodeficiency virus type 1 Tat antagonist, Ro 5-3335, predominantly inhibits transcription initiation from the viral promoter.	1995-04	7884917
Cell type-specific anti-human immunodeficiency virus type 1 activity of the transactivation inhibitor Ro5-3335.	1992-12	1282790
Discovery and characterization of an HIV-1 Tat antagonist.	1992-05	1397654
Inhibition of HIV replication in acute and chronic infections in vitro by a Tat antagonist.	1991-12-20	1763331

Patents

Sample Use Guides

In Vivo Use Guide

Male C57BL/6 mice (8–10 weeks old) received an intraperitoneal injection of the RUNX1 inhibitor, Ro 5-3335 (5 mg/kg), with 5% DMSO in PBS or 5% DMSO in PBS for 3 h, following by an intraperitoneal injection with a lethal (20 mg/kg) or sublethal dose (10 mg/kg) of LPS to induce LPS shock as described previously. Treatment with the RUNX1 inhibitor, Ro 5-3335, protected mice from LPS-induced endotoxic shock and substantially reduced the IL-6 levels.

Route of Administration: Intraperitoneal

In Vitro Use Guide

Ro 5-3335 inhibited HIV-1 replication (IC50 = 0.1-1 microM) by reducing viral RNA synthesis in acutely, as well as chronically, infected cells in vitro. Ro 5-3335 selectively reduces viability of human CBF leukemia cells in culture with IC50 values in micromolar range.

Name

Type

Language

RO-5-3335

Common Name

English

NSC-66020

Preferred Name

English

2H-1,4-BENZODIAZEPIN-2-ONE, 7-CHLORO-1,3-DIHYDRO-5-(1H-PYRROL-2-YL)-

Systematic Name

English

Code System Code Type Description

CAS

30195-30-3