Acute Lymphoblastic Leukemia

Ponatinib (AP24534) is an orally active multi-targeted kinase inhibitor with IC₅₀s of 0.37 nM, 1.1 nM, 1.5 nM, 2.2 nM, and 5.4 nM for Abl, PDGFRα, VEGFR2, FGFR1, and Src, respectively.

Palbociclib (PD 0332991) hydrochloride is an orally active selective CDK4 and CDK6 inhibitor with IC₅₀ values of 11 and 16 nM, respectively. Palbociclib hydrochloride has potent anti-proliferative activity and induces cell cycle arrest in cancer cells. Palbociclib hydrochloride can be used in the research of HR-positive and HER2-negative breast cancer and hepatocellular carcinoma.

GCN2iB is an ATP-competitive, selective GCN2 inhibitor with an IC₅₀ of 2.4 nM. GCN2iB inhibits the activation of the GCN2 pathway and upregulates GPX4. GCN2iB enhances the anticancer effect of ASNase against acute lymphoblastic leukemia. GCN2iB increases left ventricular ejection fraction, while reducing fasting blood glucose and myocardial fibrosis. GCN2iB can be used in research related to acute lymphoblastic leukemia, acute myeloid leukemia and diabetic cardiomyopathy.

6-Mercaptopurine is a purine analogue which acts as an antagonist of the endogenous purines and has been widely used as antileukemic agent and immunosuppressive drug.

Pentoxifylline (BL-191), a haemorheological agent, is an orally active non-selective phosphodiesterase (PDE) inhibitor, with immune modulation, anti-inflammatory, hemorheological, anti-fibrinolytic and anti-proliferation effects. Pentoxifylline can be used for the research of peripheral vascular disease, cerebrovascular disease and a number of other conditions involving a defective regional microcirculation.

Tolinapant (ASTX660) is an orally active cIAP1/2 and XIAP antagonist, with an IC₅₀ of < 40 nM against XIAP and an IC₅₀ of <12 nM against cIAP1. Tolinapant triggers TNFα-dependent Apoptosis in cancer cells. Tolinapant inhibits tumor growth in mouse xenograft models. Tolinapant can be used in research related to breast cancer, melanoma, lymphoma, multiple myeloma, acute lymphoblastic leukemia and advanced solid tumors.

Inotuzumab (Humanized Anti-CD22 Recombinant Antibody) is a humanized IgG4κ antibody that targets human CD22. Inotuzumab can be linked to a toxic agent Ozogamicin as an antibody-drug conjugate (ADC), Inotuzumab ozogamicin (HY-P9959). Inotuzumab can be used for the research of acute lymphoblastic leukemia and non-Hodgkin lymphoma.

FPFT-2216 is an orally active Molecular glue degrader targeting IKZF1, IKZF3, CK-1α, and PDE6D, with a DC₅₀ of 8 nM against PDE6D. FPFT-2216 mediates ubiquitin-proteasome degradation via the CRL4^CRBN E3 ubiquitin ligase complex and interacts with the non-isoprenoid-binding region of PDE6D. FPFT-2216 activates the p53 signaling pathway, inhibits the CBM complex/NF-κB pathway, upregulates IL-2, suppresses IL-1β and IL-6, and induces tumor cell Apoptosis. FPFT-2216 exhibits anticancer activity against multiple myeloma and lymphoma. FPFT-2216 can be used in research related to multiple myeloma, lymphoma, acute lymphoblastic leukemia, acute myeloid leukemia, pancreatic ductal adenocarcinoma, non-small cell lung cancer, and gastric adenocarcinoma.

Basiliximab (CHI 621) is a recombinant chimeric murine/human IgG1 monoclonal anti-interleukin-2 receptor antibody. Basiliximab can be used for the research of renal transplantation.

10-Gingerol is an AMPK agonist, which is found in the ginger oleoresin from fresh rhizome with anti-inflammatory, antioxidant and anti-proliferative activities. 10-Gingerol suppresses neointimal hyperplasia and inhibits vascular smooth muscle cell proliferation. 10-Gingerol exhibits substantial scavenging activities with an IC₅₀ value of 10.47 μM against DPPH radical, an IC₅₀ value of 1.68 μM against superoxide radical and an IC₅₀ value of 1.35 μM against hydroxyl radical. 10-Gingerol inhibits the proliferation of MDA-MB-231 tumor cell line with an IC₅₀ of 12.1 μM. 10-Gingerol suppresses the proliferation, migration, invasion, and induced apoptosis through targeting the PI3K/Akt signaling pathway in MDA-MB-231/IR cells. 10-Gingerol can be used in research on various common cancers such as ovarian cancer and colon cancer, as well as colitis and neurodegenerative diseases.

Daratumumab (PBS) (Anti-Human CD38) is the first-in-class human-specific anti-CD38 monoclonal antibody (IgG1). Daratumumab (PBS) has anti-multiple myeloma (MM) effect. Daratumumab (PBS) impairs MM cell adhesion, which results in an increased sensitivity of MM to proteasome inhibition.

QCA570 is a pan-BET-BRD PROTAC degrader. QCA570 degrades BRD2/3/4 and BRDT via cereblon and the ubiquitin-proteasome pathway, inhibits the expression of c-MYC, EZH2 and Mcl-1, induces tumor cell apoptosis, cycle arrest and regression, and exerts a synergistic inhibitory effect on Osimertinib (HY-15772)-resistant EGFR-mutant non-small cell lung cancer. QCA570 can be used in the research of acute myeloid leukemia, acute lymphoblastic leukemia, bladder cancer and non-small cell lung cancer.

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.

KI-CDK9d-32 is a selective CDK9 PROTAC degrader (IC₅₀ = 3 nM; DC₅₀ = 0.89 nM). KI-CDK9d-32 induces CDK9 degradation via the ubiquitin-proteasome pathway to abrogates CDK9 enzymatic and scaffolding functions, downregulates MYC expression and MYC-dependent signaling, represses TNF-alpha signaling pathways activity and pre-rRNA levels. KI-CDK9d-32 disrupts nucleolar homeostasis, blocks cell cycle progression and cellular translation by reducing 4EBP1 phosphorylation, and elicits cancer cell cytotoxicity in a CRBN-dependent manner, while high ABCB1 activity attenuates the efficacy. KI-CDK9d-32 can be used for the research of acute lymphoblastic leukemia, rhabdomyosarcoma, pancreatic adenocarcinoma.

SK-3-91 is a multi-kinase PROTAC degrader that induces the degradation of the maximum number of unique kinases (over 125 distinct kinases) simultaneously. SK-3-91 induces protein degradation via the ubiquitin biotinylation (E-STUB) pathway, such as inducing the degradation of YTHDF2. SK-3-91 also inhibits cell proliferation and induces cell morphological changes. SK-3-91 can be used in research related to acute lymphoblastic leukemia, multiple myeloma, neuroblastoma, ovarian cancer, mantle cell lymphoma, and gastric cancer.

YX-2-107 is a PROTAC (IC₅₀= 4.4 nM) that selectively degrades CDK6. YX-2-107 effectively inhibits RB phosphorylation and FOXM1 expression in vitro and inhibits the development of Ph⁺ ALL in rats. YX-2-107 can be used in the study of Ph chromosome-positive (Ph⁺) acute lymphoblastic leukemia (ALL).

Ergolide is an orally active dual inhibitor targeting NF-κB/p65 and NLRP3. Ergolide blocks the NF-κB signaling pathway and the nuclear translocation of p65, and irreversibly binds to the NACHT domain of NLRP3 to inhibit inflammasome assembly. Ergolide significantly reduces the production of inflammatory mediators (e.g., NO, PGE₂) and cytokines, induces cancer cell apoptosis, autophagy and ROS generation. Ergolide also enhances the anti-tumor effect of vincristine. Ergolide alleviates acute lung injury via an NLRP3-dependent mechanism, and effectively improves the survival rate and behavioral function of septic mice and inflammatory zebrafish models. Ergolide is used in the research of metastatic uveal melanoma, neurodegenerative diseases (such as Alzheimer's disease, Parkinson's disease), sepsis and acute lymphoblastic leukemia.

JWZ-5-13 is a CDK7 PROTAC degrader. JWZ-5-13 inhibits the proliferation of cancer cells. JWZ-5-13 is applicable to the research of ovarian cancer, diffuse large B-cell lymphoma, acute T-lymphoblastic leukemia and non-small cell lung cancer.

XZ739 is a potent and selective BCL-XL PROTAC degrader with a DC₅₀ of 2.5 nM. XZ739 recruits CRBN to ubiquitinate and degrade BCL-XL via the ubiquitin-proteasome system. XZ739 also induces cell cycle arrest and caspase-mediated apoptosis. XZ739 can be used in research related to T-cell acute lymphoblastic leukemia and cholangiocarcinoma.