Belumosudil
- Product Name
- Belumosudil
- CAS No.
- 911417-87-3
- Chemical Name
- Belumosudil
- Synonyms
- belumosudil;KD-025;SLx2119;CS-1555;SLx 2119;SLx-2119;Rezurock;SLx-2119(KD-025);KD025 (SLx-2119);ROCK inhibitor 2
- CBNumber
- CB82624291
- Molecular Formula
- C26H24N6O2
- Formula Weight
- 452.51
- MOL File
- 911417-87-3.mol
Belumosudil Property
- Melting point:
- >228oC (dec.)
- Boiling point:
- 682.6±55.0 °C(Predicted)
- Density
- 1.318±0.06 g/cm3(Predicted)
- storage temp.
- 2-8°C(protect from light)
- solubility
- Soluble in DMSO (25 mg/ml)
- pka
- 13?+-.0.40(Predicted)
- form
- solid
- color
- White
- Stability:
- Stable for 1 year as supplied from date of purchase. Solutions in DMSO may be stored at -20°C for up to 1 month.
- InChIKey
- GKHIVNAUVKXIIY-UHFFFAOYSA-N
- SMILES
- C(NC(C)C)(=O)COC1=CC=CC(C2=NC(NC3C=CC4=C(C=3)C=NN4)=C3C(=N2)C=CC=C3)=C1
Hazard and Precautionary Statements (GHS)
- Symbol(GHS)
-
- Signal word
- Warning
- Hazard statements
-
H315Causes skin irritation
H319Causes serious eye irritation
H335May cause respiratory irritation
- Precautionary statements
-
P261Avoid breathing dust/fume/gas/mist/vapours/spray.
P264Wash hands thoroughly after handling.
P264Wash skin thouroughly after handling.
P271Use only outdoors or in a well-ventilated area.
P280Wear protective gloves/protective clothing/eye protection/face protection.
P302+P352IF ON SKIN: wash with plenty of soap and water.
P304+P340IF INHALED: Remove victim to fresh air and Keep at rest in a position comfortable for breathing.
P305+P351+P338IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continuerinsing.
P312Call a POISON CENTER or doctor/physician if you feel unwell.
P362Take off contaminated clothing and wash before reuse.
P403+P233Store in a well-ventilated place. Keep container tightly closed.
P501Dispose of contents/container to..…
N-Bromosuccinimide Price
- Product number
- 17055
- Product name
- KD025
- Purity
- ≥98%
- Packaging
- 50mg
- Price
- $236
- Updated
- 2024/03/01
- Product number
- 17055
- Product name
- KD025
- Purity
- ≥98%
- Packaging
- 100mg
- Price
- $413
- Updated
- 2024/03/01
- Product number
- 17055
- Product name
- KD 025
- Purity
- ≥98%
- Packaging
- 1mg
- Price
- $49
- Updated
- 2021/12/16
- Product number
- 17055
- Product name
- KD 025
- Purity
- ≥98%
- Packaging
- 5mg
- Price
- $221
- Updated
- 2021/12/16
- Product number
- 17055
- Product name
- KD 025
- Purity
- ≥98%
- Packaging
- 10mg
- Price
- $59
- Updated
- 2024/03/01
Belumosudil Chemical Properties,Usage,Production
Description
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.
Uses
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).
Indications
Belumosudil is an orally active drug approved for the treatment of chronic graft-versus-host disease (cGVHD). cGVHD is a chronic inflammatory disease that occurs in patients who have undergone allogeneic haematopoietic cell transplantation (allo-HCT), resulting in long-term multi-organ complications.
brand name
Rezurock
General Description
Class: serine-threonine kinase; Treatment: chronic GVHD; Other name: SLx-2119, KD025; Oral bioavailability = 64%; Elimination half-life = 19 h; Protein binding = 99.9%
Mechanism of action
Belumosudil is a Rho-associated coiled-coil-containing protein kinase-2 (ROCK2) inhibitor. Inhibition of ROCK2 reduces cytokine production through down-regulation of signal transduction and activation of phosphorylation of transcription factor 3 (STAT3). In addition, Belumosudil promotes the production of regulatory T cells by upregulating the phosphorylation of STAT5. These effects contribute to the reduction of symptoms in patients with cGVHD.
Synthesis
Belumosudil was synthesised as follows: bromoacetyl bromide (17.1) was reacted with isopropylamine (17.2) to form amide 17.3. Subsequent bromine substitution using methyl 3-hydroxybenzoate (17.4) formed ether 17.5. Saponification of the ester yielded carboxylic acid 17.6, which was converted to a chloroform using oxalyl chloride, and was subsequently reacted with 2-amino benzamide ( 17.7) to form amide 17.8. the ring was buckled under strong alkaline conditions to form quinazolinone 17.9, which was then chlorinated to 4-chloroquinazoline 17.10 using sulfoxide chloride. the final reaction was a direct SNAr reaction using 5-aminoindolazole (17.11), which completed the synthesis of belumosidul. the synthesis of belumosudil was completed using oxalyl chloride to convert the carboxylic acid 17.6 to a chloride. The final step of converting belumosudil to methanesulfonate is not described in the patent, but may have been achieved by treatment with methanesulfonic acid 17.
target
Primary target: ROCK2
References
[1] MARJAN BOERMA. Comparative gene expression profiling in three primary human cell lines after treatment with a novel inhibitor of Rho kinase or atorvastatin.[J]. Blood Coagulation & Fibrinolysis, 2008, 19 7: 709-718. DOI:10.1097/mbc.0b013e32830b2891
[2] ALEXANDRA ZANIN-ZHOROV. Selective oral ROCK2 inhibitor down-regulates IL-21 and IL-17 secretion in human T cells via STAT3-dependent mechanism.[J]. Proceedings of the National Academy of Sciences of the United States of America, 2014, 111 47: 16814-16819. DOI:10.1073/pnas.1414189111
[3] R. FLYNN. Targeted Rho-associated kinase 2 inhibition suppresses murine and human chronic GVHD through a Stat3-dependent mechanism.[J]. Blood, 2016, 127 17 1: 2144-2154. DOI:10.1182/blood-2015-10-678706
[4] MADAN JAGASIA. ROCK2 Inhibition With Belumosudil (KD025) for the Treatment of Chronic Graft-Versus-Host Disease.[J]. Journal of Clinical Oncology, 2021, 39 17: 1888-1898. DOI:10.1200/jco.20.02754
[5] DUY TRONG VIEN DIEP. Anti-adipogenic effects of KD025 (SLx-2119), a ROCK2-specific inhibitor, in 3T3-L1 cells.[J]. Scientific Reports, 2018: 2477. DOI:10.1038/s41598-018-20821-3
[6] DUY TRONG VIEN DIEP. KD025 (SLx-2119) suppresses adipogenesis at intermediate stage in human adipose-derived stem cells.[J]. Adipocyte, 2019: 114-124. DOI:10.1080/21623945.2019.1590929
[7] LEI WEI. ROCK2 inhibition enhances the thermogenic program in white and brown fat tissue in mice[J]. FASEB Journal, 2019, 34 1: 474-493. DOI:10.1096/fj.201901174rr
[8] NHU NGUYEN QUYNH TRAN K H C. ROCK2-Specific Inhibitor KD025 Suppresses Adipocyte Differentiation by Inhibiting Casein Kinase 2.[J]. Molecules, 2021, 26 16. DOI:10.3390/molecules26164747
Belumosudil Preparation Products And Raw materials
Raw materials
Preparation Products
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View Lastest Price from Belumosudil manufacturers
- Product
- SLx-2119 911417-87-3
- Price
- US $0.00/kg
- Min. Order
- 1kg
- Purity
- 99%
- Supply Ability
- 2000ton
- Release date
- 2023-08-29