General
Preferred name
DELAMANID
Synonyms
OPC-67683 ()
Delamanid D4 ()
OPC-67683 D4 ()
Opc 67683 ()
Deltyba ()
P&D ID
PD073682
CAS
681492-22-8
Tags
available
prodrug
drug
Approved by
PMDA
EMA
First approval
2013
Drug Status
investigational
approved
Drug indication
Multi-drug resistant tuberculosis
Mycobacterium infection
Max Phase
Phase 4
Probe control
Probe control not defined
Orthogonal probes
0
No orthogonal probes found
Similar probes
0
No structurally similar probes found
Structure
P&D probe-likeness score
Structure formats
[[ format ]]
[[ compound[format === 'MOL' ? 'molblock' : format.toLowerCase()] ]]
Description
(extracted from source data)
TOXICITY
While there have been no cases of delamanid overdose, some adverse reactions were observed at a higher frequency and the rate of QT prolongation increased in a dose-related manner. Treatment of overdose should involve immediate measures to remove delamanid from the gastrointestinal tract and supportive care as required. Frequent ECG monitoring should be performed [L1407].; ; Studies of genotoxicity and carcinogenic potential reveal no significant effects on humans. Delamanid and/or its metabolites have the potential to affect cardiac repolarisation via blockade of hERG potassium channels. During repeat-dose studies in dogs, foamy macrophages were observed in lymphoid tissue of various organs with delamanid treatment although clinical relevance of this finding was not established. Repeat-dose toxicity studies in rabbits revealed an inhibitory effect of delamanid and/or its metabolites on clotting factors II, VII, IX, and X via inhibition of vitamin K production [L1407, A31966]. Embryo-fetal toxicity was observed at maternally toxic dosages in reproductive studies involving rabbits [L1407].
METABOLISM
Delamanid predominantly undergoes metabolism by albumin and to a lesser extent, CYP3A4. [L1407]. The metabolism of delamanid may also be mediated by hepatic CYP1A1, CYP2D6, and CYP2E1 to a lesser extent [31966]. Four major metabolites (M1âM4) have been identified in plasma in patients receiving delamanid where M1 and M3 accounts for 13%â18% of the total plasma exposure in humans [A31968]. While they do not retain significant pharmacological activity, they may still contribute to QT prolongation [A31967]. This is especially true for the main metabolite of delamanid, M1 (DM-6705) [A31966, A31967].; ; Delamanid is predominantly metabolized by serum albumin to form M1 (DM-6705) via hydrolytic cleavage of the 6-nitro-2,3-dihydroimidazo[2,1-b] oxazole moiety. The formation of this major metabolite is suggested to be a crucial starting point in the metabolic pathway of delamanid [A31968]. M1 (DM-6705) can be further catalyzed by three pathways. In the first metabolic pathway, DM-6705 undergoes hydroxylation of the oxazole moiety to form M2 ((4RS,5S)-DM-6720), followed by CYP3A4-mediated oxidation of hydroxyl group and tautomerization of oxazole to an imino-ketone metabolite, M3 ((S)-DM-6718) [A31968]. The second metabolic pathway involves the hydrolysis and deamination of the oxazole amine to form M4 (DM-6704) followed by hydroxylation to M6 ((4R,5S)-DM-6721) and M7 ((4S,5S)-DM-6722) and oxidation of oxazole to another ketone metabolite, M8 ((S)-DM-6717) [A31968]. The third pathway involves the hydrolytic cleavage of the oxazole ring to form M5 (DM-6706) [A31968].
[[ p.pathway_name ]]
[[ compound.targets[tid].gene_name ]]
Cell lines
0
Organisms
4
Compound Sets
16
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[[ a.name ]]
[[ ligand_id ]]
free of charge
External IDs
24
Molecular Weight
534.17
Hydrogen Bond Acceptors
9
Hydrogen Bond Donors
0
Rotatable Bonds
8
Ring Count
5
Aromatic Ring Count
3
cLogP
4.97
TPSA
101.12
Fraction CSP3
0.4
Chiral centers
1.0
Largest ring
6.0
QED
0.3
Structural alerts
1
anil_di_alk_C(246)
c:1:c:c(:c:c:c:1-[#8]-[#6;X4])-[#7;$([#7!H0]-[#6;X4]),$([#7](-[#6;X4])-[#6;X4])]
PAINS Family A
Related compounds
Custom attributes
(extracted from source data)
Pathway
Microbiology&virology
Anti-infection
Target
Antifection
Bacterial
antibiotic
Indication
tuberculosis
MOA
bacterial cell wall synthesis inhibitor
Source data
