General
Preferred name
INCADRONIC ACID
Synonyms
Incadronate ()
incadronate disodium ()
Acide incadronique ()
Acido incadronico ()
NSC-723271 ()
P&D ID
PD016290
CAS
124351-85-5
Tags
available
drug
Approved by
PMDA
First approval
1997
Drug indication
Hypercalcaemia
Drug Status
approved
investigational
experimental
Max Phase
2.0
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)
ABSORPTION
Pharmacokinetic studies in patients with MAH have indicated linear pharmacokinetics with intravenous administration. [8]; ; In studies comparing absorption of incadronate in healthy volunteers verses volunteers with MAH plasma levels have been similar at 2 h, however at 8 h the plasma levels are three times higher in patients with MAH. This can be explained by the decrease in renal function experienced by patients with MAH. Notably, however, the plasma levels of incadronate are not as high as expected based on the reduction in renal clearance. This indicates that patients with hypercalcemia may experience enhanced bone uptake of the drug. [8]
MOA
Incadronate suppresses bone resorption by inhibiting osteoclasts. Incadronate was found to induce apoptosis in myeloma cells by S-phase cell cycle arrest via inhibition of the mevalonate (MVA) pathway and activation of the MAPK pathway. [1] Similarly, in studies looking at the potential role of incadronate as a treatment for adult T-cell leukemia, incadronate has been shown to inhibit the growth of T-cell lines infected with the human T-cell leukaemia virus by inducing apoptosis and S-phase cell cycle arrest by inhibiting the mevalonate pathway. ; ; Nitrogen containing bisphosphonates such as incandronate are known to induce apoptosis of hematopoietic tumor cells by inhibiting the Ras signaling pathway, as well as activating the Bim-mediated mitochondrial intrinsic apoptotic pathway. [5] They also induce apoptosis by inhibiting the prenylation of small G-proteins. [5]
DESCRIPTION
Incadronic acid inhibits growth of Dictyostelium discoideum with an IC50 of 1.6 ¦ÌM. Incadronic acid binds the farnesyl diphosphate synthase (FPPS) in Leishmania major with the Ki of 23 nM. Incadronic acid inhibits the bone resorption and reduces bone loss, that can be used in osteoporosis research. Incadronic acid inhibits the proliferation of cells RAW264.7, PC-3 and MCF-7 with IC50 of 48 to 228.6 ¦ÌM[1].
[[ p.pathway_name ]]
[[ compound.targets[tid].gene_name ]]
Cell lines
1
Organisms
0
Compound Sets
9
[[ a.name ]]
[[ ligand_id ]]
free of charge
External IDs
30
Molecular Weight
287.07
Hydrogen Bond Acceptors
3
Hydrogen Bond Donors
5
Rotatable Bonds
4
Ring Count
1
Aromatic Ring Count
0
cLogP
0.94
TPSA
127.09
Fraction CSP3
1.0
Chiral centers
0.0
Largest ring
7.0
QED
0.38
Structural alerts
0
No structural alerts detected
Related compounds
Custom attributes
(extracted from source data)
Target
Bacterial
Pathway
Anti-infection
Source data
