Btk Inhibitor

Ibrutinib (PCI-32765) is a selective, irreversible Btk inhibitor with an IC₅₀ of 0.5 nM.

Acalabrutinib (ACP-196) is an orally active, irreversible, and highly selective second-generation BTK inhibitor. Acalabrutinib binds covalently to Cys481 in the ATP-binding pocket of BTK. Acalabrutinib demonstrates potent on-target effects and efficacy in mouse models of chronic lymphocytic leukemia (CLL). Acalabrutinib can be used for CLL research. Acalabrutinib is a click chemistry reagent, itcontains an Alkyne group and can undergo copper-catalyzed azide-alkyne cycloaddition (CuAAc) with molecules containing Azide groups.

Pirtobrutinib (LOXO-305), a highly selective and non-covalent next generation BTK inhibitor, inhibits diverse BTK C481 substitution mutations. Pirtobrutinib causes regression of BTK-dependent lymphoma tumors in mouse xenograft models. Pirtobrutinib is also more than 300-fold selective for BTK versus 370 other kinases tested and shows no significant inhibition of non-kinase off-targets at 1 μM.

Zanubrutinib (BGB-3111) is a selective and orally active Bruton tyrosine kinase (Btk) inhibitor (IC₅₀: 0.3 nM).

Fenebrutinib (GDC-0853) is a potent, selective, orally available, and noncovalent bruton's tyrosine kinase (Btk) inhibitor with K_is of 0.91 nM, 1.6, 1.3, 12.6, and 3.4 nM for WT Btk, and the C481S, C481R, T474I, T474M mutants. Fenebrutinib has the potential for rheumatoid arthritis and systemic lupus erythematosus research.

Acalabrutinib (Calquence) maleate is an orally active, irreversible, and highly selective second-generation BTK inhibitor. Acalabrutinib binds covalently to Cys481 in the ATP-binding pocket of BTK. Acalabrutinib maleate demonstrates potent on-target effects and efficacy in mouse models of chronic lymphocytic leukemia (CLL). Acalabrutinib maleate can be used for CLL research. Acalabrutinib maleate is a click chemistry reagent, which contains an Alkyne group and can undergo copper-catalyzed azide-alkyne cycloaddition (CuAAc) with molecules containing Azide groups.

BTK-IN-47 (Compound 9e) is a covalent, selective BTK inhibitor with an IC₅₀ of 5.15 nM against BTK. BTK-IN-47 inhibits the BTK signaling pathway, induces cell cycle arrest, and activates the canonical Caspase-dependent Apoptotic pathway (promoting the cleavage of Caspase-3, Caspase-7 and PARP), without inducing necroptosis, pyroptosis or ferroptosis. BTK-IN-47 exerts dose-dependent antiproliferative activity against hematologic tumor cell lines. BTK-IN-47 exhibits dose-dependent in vivo antitumor activity in a Ramos cell xenograft model in BALB/c nude mice. BTK-IN-47 can be used for the research of hematologic malignancies.

Remibrutinib, is a potent and orally active bruton tyrosine kinase (BTK) inhibitor with an IC₅₀ value of 1 nM. Remibrutinib inhibits BTK activity with an IC₅₀ value of 0.023 μM in blood. Remibrutinib has the potential for Chronic urticaria (CU) treatment.

Tolebrutinib (SAR442168) is an orally active, selective, and blood-brain barrier-penetrant BTK inhibitor with neuroactive properties. Tolebrutinib is being investigated for use in multiple sclerosis (MS), particularly secondary progressive multiple sclerosis (SPMS)..

Zelebrudomide (NX-2127) (Compound 28) is an orally active PROTAC deggrader, targeting to Bruton’s Tyrosine Kinase (Btk). Zelebrudomide inhibits proliferation of BTK^C481S mutant TMD8 cells, more effectively than Ibrutinib (HY-10997). Zelebrudomide catalyzes the degradation of Ikaros (IKZF1) and Aiolos (IKZF3) with of 25 nM and 54 nM, respectively. Zelebrudomide stimulates T cell activation and increases IL-2 production in primary human T Cells. (Pink: BTK ligand 10 (HY-168302); Black: (R)-4-(1-(Pyrrolidin-3-ylmethyl)piperidin-4-yl)aniline (HY-168348); Blue: Thalidomide 5-fluoride (HY-W087383)

Rilzabrutinib (PRN1008) is a reversible covalent, selective and oral active inhibitor of Bruton’s Tyrosine Kinase (BTK), with an IC₅₀ of 1.3 nM.

Evobrutinib (M2951) is an orally active, potent, highly selective and irreversibly covalent BTK inhibitor, with an IC₅₀ of 8.9 nM. Evobrutinib (M2951) can be used for the research of autoimmune diseases.

Orelabrutinib (ICP-022) is a potent, orally active, and irreversible Bruton's tyrosine kinase (BTK) inhibitor with potential antineoplastic activity. Orelabrutinib prevents both the activation of the B-cell antigen receptor (BCR) signaling pathway and BTK-mediated activation of downstream survival pathways, inhibiting the growth of malignant B-cells that overexpress BTK.

Sunvozertinib (DZD9008) is a potent ErbBs (EGFR, Her2, especially mutant forms) and BTK inhibitor. Sunvozertinib shows IC₅₀s of 20.4, 20.4, 1.1, 7.5, and 80.4 nM for EGFR exon 20 NPH insertion, EGFR exon 20 ASV insertion, EGFR L858R and T790M mutations, and Her2 Exon20 YVMA, and EGFR WT A431, respectively (patent WO2019149164A1, example 52).

Tirabrutinib (ONO-4059) is an orally active Bruton’s Tyrosine Kinase (BTK) inhibitor (can cross the blood-brain barrier (BBB)), with an IC₅₀ of 6.8 nM. Tirabrutinib irreversibly and covalently binds to BTK and inhibits aberrant B cell receptor signaling. Tirabrutinib can be used in studies of autoimmune diseases and hematological malignancies.

Nemtabrutinib (ARQ 531) is a reversible non-covalent and orally active inhibitor of Bruton’s Tyrosine Kinase (BTK), with IC₅₀s of 0.85 nM and 0.39 nM for WT-BTK and C481S-BTK, respectively.

Avitinib (Abivertinib) is a third-generation, irreversible and orally active selective EGFR inhibitor, with IC₅₀ values of 0.18 nM, 0.18 nM, 7.68 nM and against EGFR L858R, EGFR T790M and wild-type EGFR. Avitinib is also a BTK inhibitor that induces apoptosis and inhibits phosphorylation of BTK in mantle cell lymphoma. Avitinib shows anticancer effects.

Spebrutinib (AVL-292; CC-292) is a covalent, orally active, and highly selective with an IC₅₀ of 0.5 nM.

Ibrutinib-biotin is a probe that consists of Ibrutinib linked to biotin via a long chain linker, extracted from patent WO2014059368A1 Compound 1-5, has an IC₅₀ of 0.755-1.02 nM for BTK.

BMX-IN-1 is a selective, irreversible inhibitor of bone marrow tyrosine kinase on chromosome X (BMX) that targets Cys⁴⁹⁶ in the BMX ATP binding domain with an IC₅₀ of 8 nM, also targets the related Bruton’s tyrosine kinase (BTK) with an IC₅₀ value of 10.4 nM, but is more than 47-656-fold less potent against Blk, JAK3, EGFR, Itk, or Tec activity.