Synonym
Poseltinib; HM 71224; HM-71224; HM71224; LY 3337641; LY3337641; LY-3337641
IUPAC/Chemical Name
N-(3-((2-((4-(4-methylpiperazin-1-yl)phenyl)amino)furo[3,2-d]pyrimidin-4-yl)oxy)phenyl)acrylamide
InChi Key
LZMJNVRJMFMYQS-UHFFFAOYSA-N
InChi Code
InChI=1S/C26H26N6O3/c1-3-23(33)27-19-5-4-6-21(17-19)35-25-24-22(11-16-34-24)29-26(30-25)28-18-7-9-20(10-8-18)32-14-12-31(2)13-15-32/h3-11,16-17H,1,12-15H2,2H3,(H,27,33)(H,28,29,30)
SMILES Code
C=CC(NC1=CC=CC(OC2=C(OC=C3)C3=NC(NC4=CC=C(N5CCN(C)CC5)C=C4)=N2)=C1)=O
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
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
Biological target:
Poseltinib is a Bruton’s tyrosine kinase (BTK) inhibitor with IC50 =1.95 nM.
In vitro activity:
To characterize the inhibitory effect of HM71224 on the BCR signaling pathway, the activation of BTK and PLCγ2, the physiological substrate of BTK, following stimulation with anti-IgM was examined in human Ramos B lymphoma cells. HM71224 blocked both autophosphorylation of BTK and phosphorylation of PLCγ2 with IC50 values of less than 10 nM (Fig. 1a). To explore the inhibitory effect of HM71224 on the FcγR signaling cascade, the production of the inflammatory cytokines TNF-α and IL-6 was evaluated following stimulation with anti-IgG in human monocyte THP-1 cells. Production of both TNF-α and IL-6 effectively decreased in a dose-dependent manner (Fig. 1b and c).
Reference: Arthritis Res Ther. 2017 Sep 26;19(1):211. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5615432/
In vivo activity:
HM71224 had therapeutic effects related to the amelioration of kidney damage caused by lupus-like renal inflammation. Intrarenal B cells can contribute to renal damage and inflammation by enhancing the immunological response as antigen-presenting cells, inducing cytokine-promoting T cell proliferation and lymphatic angiogenesis, and enhancing the local immune response to persisting autoantigens in the tubulointerstitium. In both MRL/lpr and NZB/W F1 mice, activation of TLR9 caused accelerated LN. On the other hand, LN develops via unique mechanisms in each strain like the highly heterogenous nature of SLE. NZB/W F1 mice promote the renal damages B cell dependent manner including secretion of autoantibody, whereas MRL/lpr mice develop the renal damages via antigen presentation and cytokine production by B cells, not secretion of autoantibodies. HM71224 markedly reduced splenic B cell numbers, including those of germinal center B cells, plasma B cells, and activated B cells. HM71224 also had inhibiroty effects on BCR and FcR signaling. These mechanisms of action of HM71224 might lead to significant amelioration of renal injury and lymphocyte infiltration in both animal models, although differences in strains in the pathogenesis of LN can lead to different degrees of therapeutic drug efficacy. It is possible that the therapeutic effects of HM71224 in glomerulonephritis, interstitial nephritis, and vessel inflammation in murine LN were mediated by B cell inhibition.
Reference: Arthritis Res Ther. 2017 Sep 26;19(1):211. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5615432/
|
Solvent |
mg/mL |
mM |
comments |
| Solubility |
| DMSO |
100.0 |
212.53 |
|
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
470.53
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. Kim YY, Park KT, Jang SY, Lee KH, Byun JY, Suh KH, Lee YM, Kim YH, Hwang KW. HM71224, a selective Bruton's tyrosine kinase inhibitor, attenuates the development of murine lupus. Arthritis Res Ther. 2017 Sep 26;19(1):211. doi: 10.1186/s13075-017-1402-1. PMID: 28950886; PMCID: PMC5615432.
In vitro protocol:
1. Kim YY, Park KT, Jang SY, Lee KH, Byun JY, Suh KH, Lee YM, Kim YH, Hwang KW. HM71224, a selective Bruton's tyrosine kinase inhibitor, attenuates the development of murine lupus. Arthritis Res Ther. 2017 Sep 26;19(1):211. doi: 10.1186/s13075-017-1402-1. PMID: 28950886; PMCID: PMC5615432.
In vivo protocol:
1. Kim YY, Park KT, Jang SY, Lee KH, Byun JY, Suh KH, Lee YM, Kim YH, Hwang KW. HM71224, a selective Bruton's tyrosine kinase inhibitor, attenuates the development of murine lupus. Arthritis Res Ther. 2017 Sep 26;19(1):211. doi: 10.1186/s13075-017-1402-1. PMID: 28950886; PMCID: PMC5615432.
1: Yu X, Guo WH, Lin H, Cheng R, Monroy EY, Jin F, Ding L, Lu D, Qi X, Wang MC, Wang J. Discovery of a potent BTK and IKZF1/3 triple degrader through reversible covalent BTK PROTAC development. Curr Res Chem Biol. 2022;2:100029. doi: 10.1016/j.crchbi.2022.100029. Epub 2022 May 17. PMID: 36712232; PMCID: PMC9879287.
2: Byun JY, Koh YT, Jang SY, Witcher JW, Chan JR, Pustilnik A, Daniels MJ, Kim YH, Suh KH, Linnik MD, Lee YM. Target modulation and pharmacokinetics/pharmacodynamics translation of the BTK inhibitor poseltinib for model-informed phase II dose selection. Sci Rep. 2021 Sep 21;11(1):18671. doi: 10.1038/s41598-021-98255-7. PMID: 34548595; PMCID: PMC8455565.
3: Genovese MC, Spindler A, Sagawa A, Park W, Dudek A, Kivitz A, Chao J, Chan LSM, Witcher J, Barchuk W, Nirula A. Safety and Efficacy of Poseltinib, Bruton's Tyrosine Kinase Inhibitor, in Patients With Rheumatoid Arthritis: A Randomized, Double-blind, Placebo-controlled, 2-part Phase II Study. J Rheumatol. 2021 Jul;48(7):969-976. doi: 10.3899/jrheum.200893. Epub 2020 Dec 15. PMID: 33323529.
