Synonym
RO-9021; RO 9021; RO9021.
IUPAC/Chemical Name
6-[(1R,2S)-2-Amino-cyclohexylamino]-4-(5,6-dimethyl-pyridin-2-ylamino)-pyridazine-3-carboxylic acid amide
InChi Key
XJZVCDVZCRLIKN-QWHCGFSZSA-N
InChi Code
InChI=1S/C18H25N7O/c1-10-7-8-15(21-11(10)2)23-14-9-16(24-25-17(14)18(20)26)22-13-6-4-3-5-12(13)19/h7-9,12-13H,3-6,19H2,1-2H3,(H2,20,26)(H2,21,22,23,24)/t12-,13+/m0/s1
SMILES Code
O=C(C1=NN=C(N[C@H]2[C@@H](N)CCCC2)C=C1NC3=NC(C)=C(C)C=C3)N
Purity
>98% (or refer to the Certificate of Analysis)
Shipping Condition
Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition
Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility
Soluble in DMSO, not in water
Shelf Life
>2 years if stored properly
Drug Formulation
This drug may be formulated in DMSO
Stock Solution Storage
0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code
2934.99.9001
More Info
Spleen tyrosine kinase (SYK) is a key integrator of intracellular signals triggered by activated immunoreceptors, including Bcell receptors (BCR) and Fc receptors, which are important for the development and function of lymphoid cells. Given the clinical efficacy of Bcell depletion in the treatment of rheumatoid arthritis and multiple sclerosis, pharmacological modulation of Bcells using orally active small molecules that selectively target SYK presents an attractive alternative therapeutic strategy.
Biological target:
RO9021 is an inhibitor of spleen tyrosine kinase (Syk; IC50 = 5.6 nM).1 It is selective for Syk over a panel of 392 other kinases at 1 µM. RO9021 also inhibits M. tuberculosis serine/threonine protein kinase G (PknG; IC50 = 4.4 µM).2 It inhibits the proliferation of, and induces apoptosis in, primary acute myeloid leukemia (AML) cells when used at a concentration of 5 µM.3 RO0921 prevents RANKL- and M-CSF-induced osteoclastogenesis in isolated mouse bone marrow-derived macrophages (BMDMs; IC50 = 145 nM).1 It reduces disease severity in a mouse model of collagen-induced arthritis when administered at doses of 5 or 45 mg/kg.
In vitro activity:
In vitro assays of protein kinase G (PknG) activity showed that RO9021 inhibits kinase activity similarly to AX20017, a known inhibitor. The inhibitory effect was found to be dose dependent with a relative IC50 value of 4.4 ± 1.1 μM. This study supports investigating RO9021 as a drug candidate for new anti-tuberculosis drugs.
Reference: ACS Omega. 2022 May 31;7(23):20204-20218. https://pubmed.ncbi.nlm.nih.gov/35721990/
In vivo activity:
To be determined
|
Solvent |
mg/mL |
mM |
| Solubility |
| DMSO |
20.0 |
56.27 |
| DMF |
20.0 |
56.27 |
Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.
Preparing Stock Solutions
The following data is based on the
product
molecular weight
355.45
Batch specific molecular weights may vary
from batch to batch
due to the degree of hydration, which will
affect the solvent
volumes required to prepare stock solutions.
| Concentration / Solvent Volume / Mass |
1 mg |
5 mg |
10 mg |
| 1 mM |
1.15 mL |
5.76 mL |
11.51 mL |
| 5 mM |
0.23 mL |
1.15 mL |
2.3 mL |
| 10 mM |
0.12 mL |
0.58 mL |
1.15 mL |
| 50 mM |
0.02 mL |
0.12 mL |
0.23 mL |
Formulation protocol:
1. Arica-Sosa A, Alcántara R, Jiménez-Avalos G, Zimic M, Milón P, Quiliano M. Identifying RO9021 as a Potential Inhibitor of PknG from Mycobacterium tuberculosis: Combinative Computational and In Vitro Studies. ACS Omega. 2022 May 31;7(23):20204-20218. doi: 10.1021/acsomega.2c02093. PMID: 35721990; PMCID: PMC9201901.
2. Liao C, Hsu J, Kim Y, Hu DQ, Xu D, Zhang J, Pashine A, Menke J, Whittard T, Romero N, Truitt T, Slade M, Lukacs C, Hermann J, Zhou M, Lucas M, Narula S, DeMartino J, Tan SL. Selective inhibition of spleen tyrosine kinase (SYK) with a novel orally bioavailable small molecule inhibitor, RO9021, impinges on various innate and adaptive immune responses: implications for SYK inhibitors in autoimmune disease therapy. Arthritis Res Ther. 2013 Oct 4;15(5):R146. doi: 10.1186/ar4329. PMID: 24286216; PMCID: PMC3978604.
In vitro protocol:
1. Arica-Sosa A, Alcántara R, Jiménez-Avalos G, Zimic M, Milón P, Quiliano M. Identifying RO9021 as a Potential Inhibitor of PknG from Mycobacterium tuberculosis: Combinative Computational and In Vitro Studies. ACS Omega. 2022 May 31;7(23):20204-20218. doi: 10.1021/acsomega.2c02093. PMID: 35721990; PMCID: PMC9201901.
2. Liao C, Hsu J, Kim Y, Hu DQ, Xu D, Zhang J, Pashine A, Menke J, Whittard T, Romero N, Truitt T, Slade M, Lukacs C, Hermann J, Zhou M, Lucas M, Narula S, DeMartino J, Tan SL. Selective inhibition of spleen tyrosine kinase (SYK) with a novel orally bioavailable small molecule inhibitor, RO9021, impinges on various innate and adaptive immune responses: implications for SYK inhibitors in autoimmune disease therapy. Arthritis Res Ther. 2013 Oct 4;15(5):R146. doi: 10.1186/ar4329. PMID: 24286216; PMCID: PMC3978604.
In vivo protocol:
To be determined
1: Arica-Sosa A, Alcántara R, Jiménez-Avalos G, Zimic M, Milón P, Quiliano M. Identifying RO9021 as a Potential Inhibitor of PknG from Mycobacterium tuberculosis: Combinative Computational and In Vitro Studies. ACS Omega. 2022 May 31;7(23):20204-20218. doi: 10.1021/acsomega.2c02093. PMID: 35721990; PMCID: PMC9201901.
2: Tang S, Yu Q, Ding C. Investigational spleen tyrosine kinase (SYK) inhibitors for the treatment of autoimmune diseases. Expert Opin Investig Drugs. 2022 Mar;31(3):291-303. doi: 10.1080/13543784.2022.2040014. Epub 2022 Feb 18. PMID: 35130124.
3: Liao C, Hsu J, Kim Y, Hu DQ, Xu D, Zhang J, Pashine A, Menke J, Whittard T, Romero N, Truitt T, Slade M, Lukacs C, Hermann J, Zhou M, Lucas M, Narula S, DeMartino J, Tan SL. Selective inhibition of spleen tyrosine kinase (SYK) with a novel orally bioavailable small molecule inhibitor, RO9021, impinges on various innate and adaptive immune responses: implications for SYK inhibitors in autoimmune disease therapy. Arthritis Res Ther. 2013 Oct 4;15(5):R146. doi: 10.1186/ar4329. PMID: 24286216; PMCID: PMC3978604.
4: Brattås MK, Hemsing AL, Rye KP, Hatfield KJ, Reikvam H. Heterogeneity of Patient-Derived Acute Myeloid Leukemia Cells Subjected to SYK In Vitro Inhibition. Int J Mol Sci. 2022 Nov 25;23(23):14706. doi: 10.3390/ijms232314706. PMID: 36499034; PMCID: PMC9737311.
