JAK Degrader

TL12-186 is a multi-kinase PROTAC degrader. TL12-186 recruits the CRBN E3 ubiquitin ligase to target and degrade a variety of distinct kinases, including FLT3, BTK, AURKA, PTK2B, and multiple cyclin-dependent kinases (CDKs). TL12-186 can be used in leukemia-related research.

SJ10542 is a potent and selective JAK2/3 PROTAC degrader, with DC₅₀ values of 14 nM and 11 nM against JAK2 and JAK3, respectively. SJ10542 exhibits anti-tumor activity and can be used for research on acute lymphoblastic leukemia.

SJ988497 is a PROTAC degrader targeting JAK2. SJ988497 induces the proteasomal degradation of CRBN-mediated JAK2, JAK1, JAK3, GSPT1, and IKZF1, and functions as a CRBN neosubstrate for GSPT1. SJ988497 retains binding affinity for the kinase domain of JAK2. SJ988497 can be used in studies related to cancers such as crlf2-rearranged acute lymphoblastic leukemia.

PROTAC TYK2 degrader-2 is a potent and subtype-selective TYK2 degrader. PROTAC TYK2 degrader-2 has TYK2 degradation activity with DC₅₀ value of 14 nM. PROTAC TYK2 degrader-2 can be used for the research of autoimmune disease.

PROTAC JAK1 degrader 1 is a JAK1 PROTAC degrader with a DC₅₀ of 214 nM and an IC₅₀ of 5.2 nM. PROTAC JAK1 degrader 1 inhibits the downstream JAK-STAT signaling pathway by degrading JAK1. PROTAC JAK1 degrader 1 exhibits antiproliferative activity in cells. PROTAC JAK1 degrader 1 can be used for research on leukemia.

PROTAC TYK2 degrader-1 is a TYK2 PROTAC degrader with a D_max ≥ 60%. PROTAC TYK2 degrader-1 reduces the phosphorylation levels of IFNα-induced STAT1 (Tyr701) and STAT3 (Tyr705) in immune cells. PROTAC TYK2 degrader-1 can be used in research on cancer, inflammatory diseases, etc.

TYD-68 is a CRBN-recruiting TYK2 PROTAC degrader with a DC₅₀ of 0.42 nM, and displays selectivity against JAK1/JAK2-dependent signaling pathways. TYD-68 inhibits TYK2-mediated signaling, exerts therapeutic efficacy in murine psoriasis models, reduces PASI scores, downregulates TYK2 protein levels and decreases the secretion of proinflammatory cytokines, TYD-68 can be used for the study of psoriasis and other TYK2-driven autoimmune diseases.

PROTAC JAK1/2 degrader-1 is an orally active JAK1/JAK2 PROTAC degrader, with DC₅₀ values of 1.4 μM and 0.92 μM against JAK1 and JAK2, respectively. PROTAC JAK1/2 degrader-1 triggers degradation via a CRBN- and proteasome-dependent pathway. PROTAC JAK1/2 degrader-1 inhibits the secretion of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6). PROTAC JAK1/2 degrader-1 alleviates inflammatory responses and colon injury by inhibiting the JAK/STAT3 signaling pathway. PROTAC JAK1/2 degrader-1 can be used for the research of inflammatory bowel disease.

SJ1008030 (compound 8) is a JAK2 PROTAC which selectively degrades JAK2. SJ1008030 inhibits MHH–CALL-4 cell growth with an IC₅₀ of 5.4 nM. SJ1008030 can be used for the research of leukemia.

YSY01A is a proteasome inhibitor that can suppress cancer cell survival by inducing apoptosis (Apoptosis). Its IC₅₀ values are 51.0 nM for HEK293T, 9.2 nM for A549, 5.2 nM for MCF-7, 8.9 nM for MGC-803, and 35.4 nM for PC-3M cells. Additionally, YSY01A eliminates constitutive STAT3 signaling by downregulating gp130 and JAK2 in human A549 lung cancer cells. YSY01A holds promise for research in the field of cancer therapy.

PROTAC FLT3/JAK2/BRD4 Degrader-1 is a FLT3/JAK2/BRD4 PROTAC degrader with DC₅₀ values of 5.23, 0.68, and 1.17 nM, respectively. PROTAC FLT3/JAK2/BRD4 Degrader-1 induces cereblon- and proteasome-dependent degradation of FLT3, JAK2, and BRD4 via the ubiquitin-proteasome system. PROTAC FLT3/JAK2/BRD4 Degrader-1 is used in studies related to FLT3 inhibitor-resistant leukemia and acute myeloid leukemia.

TYK2 ligand 3 is a TYK2 ligand that can be used for the synthesis of PROTACs, such as PROTAC TYK2 degrader-2 (HY-152227).

PROTAC JAK2 degrader-1 is a JAK2 PROTAC degrader, with a DC₅₀ of 27.35 nM. PROTAC JAK2 degrader-1 induces JAK2 degradation via the ubiquitin-proteasome pathway. PROTAC JAK2 degrader-1 inhibits the JAK2-STAT signaling pathway. PROTAC JAK2 degrader-1 induces G₂/M phase arrest and apoptosis in cancer cells. PROTAC JAK2 degrader-1 exhibits antiproliferative activity against cancer cells. PROTAC JAK2 degrader-1 inhibits recombinant human erythropoietin (rhEPO)-mediated polycythemia and splenomegaly in mice. PROTAC JAK2 degrader-1 can be used for research on myeloproliferative neoplasms, including polycythemia vera.

Jak1 RIMTAC-1 is a JAK1 RIMTAC degrader (a PROTAC-like agent) with a DC₅₀ of 322.8 nM. Jak1 RIMTAC-1 forms a ternary complex with JAK1 and RIPK1, thereby recruiting the VHL E3 ligase complex to ubiquitinate JAK1 via the ubiquitin-proteasome system and mediate its subsequent proteasomal degradation. Jak1 RIMTAC-1 does not alter JAK1 mRNA levels (pink: Jak1 ligand-1 (HY-187503); blue: RIPK1-ligand-4 (HY-187391); black: Linker (HY-B0704)).