DAPORINAD

Details

Stereochemistry	ACHIRAL
Molecular Formula	C24H29N3O2
Molecular Weight	391.506
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	1
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

O=C(NCCCCC1CCN(CC1)C(=O)C2=CC=CC=C2)\C=C\C3=CC=CN=C3

InChI

InChIKey=KPBNHDGDUADAGP-VAWYXSNFSA-N

InChI=1S/C24H29N3O2/c28-23(12-11-21-8-6-15-25-19-21)26-16-5-4-7-20-13-17-27(18-14-20)24(29)22-9-2-1-3-10-22/h1-3,6,8-12,15,19-20H,4-5,7,13-14,16-18H2,(H,26,28)/b12-11+

HIDE SMILES / InChI

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/23617784 | https://www.cancer.gov/publications/dictionaries/cancer-drug/def/daporinad | https://jamanetwork.com/journals/jamadermatology/fullarticle/2502283

Daporinad is an inhibitor of nicotinamide phosphoribosyltransferase (NMPRTase), an enzyme that participates in the biosynthesis of nicotinamide adenine dinucleotide (NAD+) from niacinamide (vitamin B3). Inhibition of NMPRTase may deplete energy reserves in metabolically active tumor cells and induce tumor cell apoptosis. In addition, this agent may inhibit tumor cell production of vascular endothelial growth factor (VEGF), resulting in the inhibition of tumor angiogenesis. Daporinad was investigated as a treatment of B-cell chronic lymphocytic leukemia, melanoma, and cutaneous T-cell lymphoma. Clinical trials have shown that drug has low efficacy when used alone.

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Nicotinamide phosphoribosyltransferase 8 Target ID: CHEMBL1744525 Sources: https://www.ncbi.nlm.nih.gov/pubmed/23617784	Inhibitor 8297		3.0 nM [IC50]

PubMed

Title	Date	PubMed
		252160019
FK866, a highly specific noncompetitive inhibitor of nicotinamide phosphoribosyltransferase, represents a novel mechanism for induction of tumor cell apoptosis.	2003 Nov 1	14612543
Crystal structure of visfatin/pre-B cell colony-enhancing factor 1/nicotinamide phosphoribosyltransferase, free and in complex with the anti-cancer agent FK-866.	2006 Sep 8	16901503
Detection and pharmacological modulation of nicotinamide mononucleotide (NMN) in vitro and in vivo.	2009 May 15	19426698
Inhibition of lactate dehydrogenase A induces oxidative stress and inhibits tumor progression.	2010 Feb 2	20133848
Nicotinamide phosphoribosyl transferase (Nampt) is a target of microRNA-26b in colorectal cancer cells.	2013	23922874
Elevated microRNA-34a in obesity reduces NAD+ levels and SIRT1 activity by directly targeting NAMPT.	2013 Dec	23834033
On-target effect of FK866, a nicotinamide phosphoribosyl transferase inhibitor, by apoptosis-mediated death in chronic lymphocytic leukemia cells.	2014 Sep 15	25172933
Retinal toxicity, in vivo and in vitro, associated with inhibition of nicotinamide phosphoribosyltransferase.	2015 Mar	25505128

Name

Type

Language

DAPORINAD

Official Name

English

APO866

Code

English

2-PROPENAMIDE, N-(4-(1-BENZOYL-4-PIPERIDINYL)BUTYL)-3-(3-PYRIDINYL)-, (2E)-

Systematic Name

English

daporinad [INN]

Common Name

English

K 22.175

Code

English

Daporinad [WHO-DD]

Common Name

English

APO-866

Code

English

FK866

Code

English

FK-866

Code

English

(2E)-N-(4-(1-BENZOYLPIPERIDIN-4-YL)BUTYL)-3-(PYRIDIN-3-YL)PROP-2-ENAMIDE

Systematic Name

English

Classification Tree Code System Code

NCI_THESAURUS

C471