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Incadronic acid

Incadronic acid structure

CAS No:
124351-85-5
Formula:
C8H19NO6P2
Chemical Name:
Incadronic acid
Synonyms:
Phosphonic acid,P,P′-[(cycloheptylamino)methylene]bis-;Phosphonic acid,[(cycloheptylamino)methylene]bis-;P,P′-[(Cycloheptylamino)methylene]bis[phosphonic acid];[(Cycloheptylamino)methylene]bis(phosphonic acid);Incadronic acid;[(Cycloheptylamino)methylene]diphosphonic acid;Cimadronic acid;Cimadronate;Icandronate
Categories:
Organic Chemistry > Phosphines

Description

Incadronic acid is a 1,1-bis(phosphonic acid).|Incadronate, or YM-175, is a nitrogen containing bisphosphonate. Along with being investigated to treat hypercalcemia of malignancy, it has also been investigated in the treatment of myeloma, leukemia, and other cancers. Incadronic acid was first described in the literature in 1991.|Incadronic Acid is a third-generation amino-bisphosphonate with anti-resorptive activity. Although the exact mechanism of action has yet to be fully elucidated, incadronic acid binds to and adsorbs onto hydroxyapatite crystals in the bone matrix, thereby preventing osteoclast resorption. This agent also binds to and inhibits farnesyl pyrophosphate synthase, an enzyme that plays an important role in the mevalonate pathway. This inhibits the formation of isoprenoids that are essential for protein prenylation. This prevents farnesylation and geranylgeranylation of proteins essential for osteoclast function, thereby leading to the induction of apoptosis of osteoclasts. By preventing osteoclast-mediated bone resorption, incadronic acid prevents bone destruction.

Incadronic acid Basic Attributes

Molecular Weight：

287.18700

Exact Mass：

287.19

UNII：

G5C4M8847E

NSC Number：

723271

DSSTox ID：

DTXSID90154283

NCI Thesaurus Code：

C65906

Characteristics

PSA：

146.71000

XLogP3：

1.32870

Density：

1.48g/cm3

Melting Point：

250-251 °C (decomp)

Boiling Point：

564.2ºC at 760mmHg

Flash Point：

295ºC

Refractive Index：

1.535

Vapor Pressure：

3.3E-14mmHg at 25°C

Drug Information

Drug Indication：

Incadronate has been investigated in the treatment of myeloma, leukemia, and other cancers. It has also been investigated in patients with hypercalcemia of malignancy.

MeSH：

Agents that inhibit BONE RESORPTION and/or favor BONE MINERALIZATION and BONE REGENERATION. They are used to heal BONE FRACTURES and to treat METABOLIC BONE DISEASES such as OSTEOPOROSIS. (See all compounds classified as Bone Density Conservation Agents.)

Absorption：

Incadronate is 55.1-69.5% eliminated in the urine as the unchanged parent drug.

Metabolism/Metabolites：

Incadronate is not metabolized in rats.

Biological Half-Life：

Incadronate has a biexponential half life. The T_1/2α is 0.26-0.40h and the T_1/2β is 1.58-1.98h.

Mechanism of Action：

Bisphosphonates are taken into the bone where they bind to hydroxyapatite. Bone resorption by osteoclasts causes local acidification, releasing the bisphosphonate, which is taken into the osteoclast by fluid-phase endocytosis. Endocytic vesicles become acidified, releasing bisphosphonates into the cytosol of osteoclasts where they act. Osteoclasts mediate resorption of bone. When osteoclasts bind to bone they form podosomes, ring structures of F-actin. Disruption of the podosomes causes osteoclasts to detach from bones, preventing bone resorption. Nitrogen containing bisphosphonates such as incandronate are known to induce apoptosis of hematopoietic tumor cells by inhibiting the components of the mevalonate pathway farnesyl diphosphate synthase, farnesyl diphosphate, and geranylgeranyl diphosphate. These components are essential for post-translational prenylation of GTP-binding proteins like Rap1. The lack of prenylation of these proteins interferes with their function, and in the case of Rap1, leads to apoptosis. incadronate also activated caspases 3, 4, and 7; further contributing to apoptosis.

MeSH Entry Terms：

cimadronate

Computed Properties

Molecular Weight:287.19
XLogP3:-3.5
Hydrogen Bond Donor Count:5
Hydrogen Bond Acceptor Count:7
Rotatable Bond Count:4
Exact Mass:287.06876132
Monoisotopic Mass:287.06876132
Topological Polar Surface Area:127
Heavy Atom Count:17
Complexity:307
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes