What is the ROCK inhibitor 2?

ROCK inhibitor 2 is , while it's Molecular Formula is C 26 H 24 N 6 O 2 . KD 025 is an inhibitor of Rho-associated protein kinase II (ROCK-II), a serine/threonine kinase that regulates the formation of actin stress fibers and focal adhesions, smooth muscle contraction, and gene expression (1, 2). KD025 has been shown to reduce infarct volume after transient middle cerebral artery occlusion (2).

What is the CAS number for ROCK inhibitor 2?

The CAS number of ROCK inhibitor 2 is 911417-87-3.

What is ROCK inhibitor 2 (911417-87-3) used for?

KD 025 is an inhibitor of Rho-associated kinase 2 (ROCK2; IC50 = 0.105 μM). It is selective for ROCK2 over ROCK1 (IC50 = 24 μM). KD 025 (10 μM) decreases the expression of connective tissue growth factor (CTGF) and induces remodeling of the actin cytoskeleton in isolated human ileal fibrotic smooth muscle cells. It inhibits heat-killed C. albicans- or S. epidermidis-induced production of IL-17 in isolated human peripheral blood mononuclear cells (PBMCs) when used at concentrations ranging from 1.25 to 10 μM. KD 025 (100 and 200 mg/kg) reduces infarct volume in a mouse model of cerebral ischemia induced by transient middle cerebral artery occlusion (MCAO). It decreases disease severity in a mouse model of sclerodermatous chronic graft versus host disease (GVHD) when administered at a dose of 150 mg/kg. Formulations containing KD 025 have been used in the treatment of chronic GVHD.

What is the ROCK inhibitor 2?

ROCK inhibitor 2 is , while it's Molecular Formula is C 26 H 24 N 6 O 2 . KD 025 is an inhibitor of Rho-associated protein kinase II (ROCK-II), a serine/threonine kinase that regulates the formation of actin stress fibers and focal adhesions, smooth muscle contraction, and gene expression (1, 2). KD025 has been shown to reduce infarct volume after transient middle cerebral artery occlusion (2).

What is the CAS number for ROCK inhibitor 2?

The CAS number of ROCK inhibitor 2 is 911417-87-3.

What is ROCK inhibitor 2 (911417-87-3) used for?

KD 025 is an inhibitor of Rho-associated kinase 2 (ROCK2; IC50 = 0.105 μM). It is selective for ROCK2 over ROCK1 (IC50 = 24 μM). KD 025 (10 μM) decreases the expression of connective tissue growth factor (CTGF) and induces remodeling of the actin cytoskeleton in isolated human ileal fibrotic smooth muscle cells. It inhibits heat-killed C. albicans- or S. epidermidis-induced production of IL-17 in isolated human peripheral blood mononuclear cells (PBMCs) when used at concentrations ranging from 1.25 to 10 μM. KD 025 (100 and 200 mg/kg) reduces infarct volume in a mouse model of cerebral ischemia induced by transient middle cerebral artery occlusion (MCAO). It decreases disease severity in a mouse model of sclerodermatous chronic graft versus host disease (GVHD) when administered at a dose of 150 mg/kg. Formulations containing KD 025 have been used in the treatment of chronic GVHD.

Product Class

911417-87-3

Product Name：Belumosudil
Molecular Formula：C26H24N6O2
Purity：99%
Molecular Weight：452.516

Inquiry

Product Details:

CasNo： 911417-87-3

Molecular Formula： C26H24N6O2

Factory Supply Belumosudil,Sale 911417-87-3 On Stock

Molecular Formula:C₂₆H₂₄N₆O₂
Molecular Weight:452.516
Boiling Point:682.6±55.0 °C(Predicted)
PKA:13?+-.0.40(Predicted)
PSA：108.31000
Density:1.318±0.06 g/cm3(Predicted)
LogP:5.73340

Belumosudil(Cas 911417-87-3) Usage

Description	Belumosudil is an oral inhibitor of Rho-associated coiled-coil-containing protein kinases (ROCK), specifically targeting ROCK2. It belongs to the class of drugs known as serine/threonine kinase inhibitors. By inhibiting ROCK2, Belumosudil modulates immune cell activity and prevents scar tissue buildup, which are key mechanisms involved in the pathogenesis of chronic GVHD.
Uses	Belumosudil is indicated for the treatment of chronic graft versus host disease (GVHD) in adults and children aged 12 years and older who have not responded to at least two other treatments. GVHD is a complication that can occur after hematopoietic stem-cell transplant (HSCT), where transplanted immune cells attack the recipient's tissues. Belumosudil helps to reduce immune cell activity and prevent tissue damage in individuals with chronic GVHD, thereby improving symptoms and quality of life.
Regulatory Approval	Ibrutinib was approved by regulatory agencies such as the FDA and the European Commission for the treatment of various blood cancers, including MCL and CLL/SLL.

911417-87-3 Relevant articles

Safety, Tolerability, and Pharmacokinetics of Belumosudil, a Selective Rho-associated Coiled-coil-containing Protein Kinase 2 Inhibitor, in Healthy Japanese Volunteers: A PhaseⅠ, Randomized, Controlled Trial

Y Ogama，H Sato，A Miyata，K Kijima，Y Kumagai

, Japanese journal of clinical pharmacology, 2023

To assess the safety, tolerability, and pharmacokinetics of belumosudil, a selective Rho-associated coiled-coil-containing protein kinase 2 inhibitor, in healthy Japanese male adults, a phase Ⅰ, randomized, double-blind, placebo-controlled trial was conducted.Methods: In the single-dose study, 200, 400, or 800 mg of belumosudil or matching placebo was orally administered to 3 separate cohorts.

Budget Impact Analysis of Belumosudil for Chronic Graft-Versus-Host Disease Treatment in the United States

Carlos Bachier 1, Jeffrey Rolf Skaar 2, Sumudu Dehipawala 2, Benjamin Miao 3, Jonathan Ieyoub 4, Haya Taitel 4

Blood, Volume 138, Supplement 1, 23 November 2021, Page 1903

Belumosudil use was modeled in three different scenarios based on projections of branded agent shares (i.e., source of share from ibrutinib only, ruxolitinib only, or both ibrutinib and ruxolitinib in a market with branded agents only).

Belumosudil for Chronic Graft-Versus-Host Disease (cGVHD) after 2 or More Prior Lines of Therapy: The Rockstar Study (KD025-213)

Corey Cutler MD MPH, FRCPC 1, Stephanie J. Lee MDMPH 2, Sally Arai MD MS 3, Marcello Rotta MD 4, Behyar Zoghi MD * 5, Aravind Ramakrishnan MD 6, David Eiznhamer PhD * 7, Olivier Schueller PhD * 8, Zhongming Yang PhD * 9, Laurie S. Green MD * 10, Sanjay K. Aggarwal MD * 8, Bruce R. Blazar MD 11, Steven Z. Pavletic MD MS 12, Madan Jagasia MBBS, MS, MMHC 13

Blood,Volume 136, Supplement 1, 5 November 2020, Pages 45-46

This phase 2, open-label, randomized, multicenter study evaluated belumosudil 200 mg QD (n=66) and BID (n=66) in patients with cGVHD who received 2 to 5 prior lines of therapy (LOT). Treatment continued until clinically significant progression of cGVHD. The primary end point was overall response rate (ORR), defined per the 2014 National Institutes of Health Consensus Criteria.

911417-87-3 Process route

: 75726-96-4
2-bromo-N-isopropylacetamide

: 911417-87-3
2-[3-[4-(1H-indazol-5-ylamino)quinazolin-2-yl]phenoxy]-N-propan-2-ylacetamide

Conditions

Conditions	Yield
Multi-step reaction with 7 steps 1: potassium carbonate / N,N-dimethyl-formamide / 2 h / 80 °C 2: sodium hydroxide / water; methanol; tetrahydrofuran / 20 °C 3: oxalyl dichloride / dichloromethane; N,N-dimethyl-formamide / 0.5 h / 20 °C / Inert atmosphere; Cooling with ice 4: N-ethyl-N,N-diisopropylamine / dichloromethane / 0.17 h / 20 °C / Cooling with ice; Inert atmosphere 5: potassium carbonate / water; ethanol / 2.5 h / 80 °C 6: thionyl chloride / N,N-dimethyl-formamide / 0.5 h / 20 °C / Inert atmosphere; Cooling with ice 7: N,N-dimethyl-formamide / 2.5 h / 100 °C / Sealed tube With thionyl chloride; oxalyl dichloride; potassium carbonate; N-ethyl-N,N-diisopropylamine; sodium hydroxide; In tetrahydrofuran; methanol; ethanol; dichloromethane; water; N,N-dimethyl-formamide;

Yield

Multi-step reaction with 7 steps

1: potassium carbonate / N,N-dimethyl-formamide / 2 h / 80 °C

2: sodium hydroxide / water; methanol; tetrahydrofuran / 20 °C

3: oxalyl dichloride / dichloromethane; N,N-dimethyl-formamide / 0.5 h / 20 °C / Inert atmosphere; Cooling with ice

4: N-ethyl-N,N-diisopropylamine / dichloromethane / 0.17 h / 20 °C / Cooling with ice; Inert atmosphere

5: potassium carbonate / water; ethanol / 2.5 h / 80 °C

6: thionyl chloride / N,N-dimethyl-formamide / 0.5 h / 20 °C / Inert atmosphere; Cooling with ice

7: N,N-dimethyl-formamide / 2.5 h / 100 °C / Sealed tube

With thionyl chloride; oxalyl dichloride; potassium carbonate; N-ethyl-N,N-diisopropylamine; sodium hydroxide; In tetrahydrofuran; methanol; ethanol; dichloromethane; water; N,N-dimethyl-formamide;

: 28144-70-9,88-68-6
anthranilic acid amide

: 911417-87-3
2-[3-[4-(1H-indazol-5-ylamino)quinazolin-2-yl]phenoxy]-N-propan-2-ylacetamide

Conditions

Conditions	Yield
Multi-step reaction with 10 steps 1.1: pyridine / chloroform / 6 h / 20 °C 2.1: sodium hydroxide / water / 4 h / Heating / reflux 2.2: 2 h / 20 °C / pH 7 3.1: boron tribromide / dichloromethane / 4 h / -78 - 20 °C 3.2: 0.5 h / -78 - 20 °C 3.3: pH 7 4.1: pyridine / 3.5 h / 105 °C 5.1: thionyl chloride; N,N-dimethyl-formamide / 4 h / Heating / reflux 6.1: isopropyl alcohol / 0.5 h / 95 °C 7.1: methanol; ammonia; water / 48 h / 20 °C 8.1: potassium carbonate / N,N-dimethyl-formamide / 3.5 h / 80 °C 9.1: trifluoroacetic acid / dichloromethane / 1 h / 20 °C 10.1: benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate; N-ethyl-N,N-diisopropylamine / dichloromethane; N,N-dimethyl-formamide / 0.25 h / 20 °C 10.2: 0.5 h / 20 °C With pyridine; methanol; sodium hydroxide; thionyl chloride; benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate; ammonia; water; boron tribromide; potassium carbonate; N-ethyl-N,N-diisopropylamine; N,N-dimethyl-formamide; trifluoroacetic acid; In dichloromethane; chloroform; water; N,N-dimethyl-formamide; isopropyl alcohol;

Yield

Multi-step reaction with 10 steps

1.1: pyridine / chloroform / 6 h / 20 °C

2.1: sodium hydroxide / water / 4 h / Heating / reflux

2.2: 2 h / 20 °C / pH 7

3.1: boron tribromide / dichloromethane / 4 h / -78 - 20 °C

3.2: 0.5 h / -78 - 20 °C

3.3: pH 7

4.1: pyridine / 3.5 h / 105 °C

5.1: thionyl chloride; N,N-dimethyl-formamide / 4 h / Heating / reflux

6.1: isopropyl alcohol / 0.5 h / 95 °C

7.1: methanol; ammonia; water / 48 h / 20 °C

8.1: potassium carbonate / N,N-dimethyl-formamide / 3.5 h / 80 °C

9.1: trifluoroacetic acid / dichloromethane / 1 h / 20 °C

10.1: benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate; N-ethyl-N,N-diisopropylamine / dichloromethane; N,N-dimethyl-formamide / 0.25 h / 20 °C

10.2: 0.5 h / 20 °C

With pyridine; methanol; sodium hydroxide; thionyl chloride; benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate; ammonia; water; boron tribromide; potassium carbonate; N-ethyl-N,N-diisopropylamine; N,N-dimethyl-formamide; trifluoroacetic acid; In dichloromethane; chloroform; water; N,N-dimethyl-formamide; isopropyl alcohol;

911417-87-3 Upstream products

911417-62-4
2-(3-(4-(1H-indazol-5-ylamino)quinazolin-2-yl)phenoxy)acetic acid
75-31-0
isopropylamine
19335-11-6
1H-indazol-5-ylamine
75726-96-4
2-bromo-N-isopropylacetamide

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