Palifosfamide

96
莫小枫
2017.11.17 13:36 字数 362

"目录号: HY-14799

Metabolic Enzyme/Protease-

Palovarotene 是一种核视网膜酸受体γ (RAR-γ) 激动剂。

RAR/RXR

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Retinoic acid-Tamibarotene-AM580-Bexarotene-Fenretinide-AGN 194310-Tazarotene-Isotretinoin-TTNPB-Acitretin-Adapalene-AGN 195183-Magnolol-(R)-Flurbiprofen-AR7-

生物活性

Description

Palovarotene is a nuclear retinoic acid receptor γ (RAR-γ) agonist.

IC50& Target

RAR-γ[1]

In Vivo

Palovarotene suppresses post-traumatic chondrogenesis and osteogenesis and mitigated trauma-induced ectopic bone formation. Palovarotene inhibits subcutaneous and intramuscular heterotopic ossification (HO) in mice. Palovarotene is given orally for 14 days at 1 mg/kg/day starting on post-operative day (POD) 1 or POD-5, and HO amount, wound dehiscence and related processes are monitored for up to 84 days post injury. Compared to vehicle-control animals, Palovarotene significantly decreases HO by 50 to 60% regardless of when the treatment started and if infection is present[1]. Starting from day 1 of injury, half of the Acvr1cR206H/+mice are treated with Palovarotene by daily gavage for 14 days and the other half received vehicle as control. Analysis by mCT and 3D image reconstruction at day 14 shows that large HO tissue masses have formed in the targeted leg of Acvr1cR206H/+mutant mice receiving vehicle, but HO formation is greatly diminished in Palovarotene-treated companions by more than 80% based on bone volume/total volume quantification[2].

Clinical Trial

NCT02521792

Clementia Pharmaceuticals Inc.

Fibrodysplasia Ossificans Progressiva

January 2016

Phase 2

NCT02979769

Clementia Pharmaceuticals Inc.

Fibrodysplasia Ossificans Progressiva

November 2016

Phase 2

NCT02279095

Clementia Pharmaceuticals Inc.

Fibrodysplasia Ossificans Progressiva

October 2014

Phase 2

NCT02190747

Clementia Pharmaceuticals Inc.

Fibrodysplasia Ossificans Progressiva

July 2014

Phase 2

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References

[1].Pavey GJ, et al. Targeted stimulation of retinoic acid receptor-γ mitigates the formation of heterotopic ossification in an established blast-related traumatic injury model. Bone. 2016 Sep;90:159-67.

[2].Chakkalakal SA, et al. Palovarotene Inhibits Heterotopic Ossification and Maintains Limb Mobility and Growth in Mice With the Human ACVR1(R206H) Fibrodysplasia Ossificans Progressiva (FOP) Mutation. J Bone Miner Res. 2016 Sep;31(9):1666-75.

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