PROTAC mHTT Degrader-1 is a blood-brain barrier-penetrant mutant huntingtin (mHTT) PROTAC degrader. PROTAC mHTT Degrader-1 specifically recognizes pathogenic mHTT aggregates and recruits Cereblon (CRBN), thereby inducing ubiquitination and proteasomal degradation of mHTT. PROTAC mHTT Degrader-1 alleviates mHTT-induced cytotoxicity and neuroinflammation. In the R6/2 Huntington's disease mouse model, PROTAC mHTT Degrader-1 reduces cerebral protein aggregation levels and improves body weight, motor coordination and survival rate of animals. PROTAC mHTT Degrader-1 can be used for research on PROTAC therapies for Huntington's disease and other neurodegenerative diseases. (Pink: Huntingtin ligand ; Blue: Cereblon ligand ; Black: linker ).

PROTAC LRRK2 Degrader-1 (compound 18) is a leucine-rich repeat kinase 2 (LRRK2) PROTAC degrader with an IC50 value less than 10 nM. PROTAC LRRK2 Degrader-1 can be used in the research of Parkinson's disease.

PROTAC hCAII degrader-1 is a potent PROTAC human carbonic anhydrase II (hCAII) degrader with an DC50 of 0.5 nM in HEK293 cells. PROTAC hCAII degrader-1 recruits cereblon (CRBN) E3 ubiquitin ligase to form a ternary complex. PROTAC hCAII degrader-1 enables ubiquitination and subsequent proteasomal degradation of hCAII. (Pink: CA Ⅱ ligand ; Blue: Cereblon ligand ; Black: linker).

PROTAC GPX4 degrader-5 (compound N15) is an efficient and highly selective PROTAC GPX4 degrader (DC50 = 28 nM). PROTAC GPX4 degrader-5 can induce ferroptosis and has low toxicity to normal cells. PROTAC GPX4 degrader-5 can significantly increase ROS. PROTAC GPX4 degrader-5 exerts anti proliferative effects on various tumor cells. PROTAC GPX4 degrader-5 is commonly used in cancer research. (Pink: GPX4 ligand ; Blue: Others ligand ; Black: linker ).

PROTAC EZH2 Degrader-44 (compound 60) is a highly efficient PROTAC degrader targeting the EZH2-PRC2 complex. By recruiting the CRBN E3 ligase and relying on the proteasome system, PROTAC EZH2 Degrader-44 simultaneously induces the degradation of core components EZH2, SUZ12 and EED, thereby significantly reducing the levels of H3K27me3 and CARM1. PROTAC EZH2 Degrader-44 exerts antiproliferative effects through a dual mechanism: on the one hand, it triggers mitochondrial dysfunction leading to decreased membrane potential; on the other hand, it strongly promotes apoptosis by regulating Bcl-2 family proteins (upregulating Bax, Caspase-3 and PARP, and downregulating Bcl-2). PROTAC EZH2 Degrader-44 exhibits only extremely low cytotoxicity in human normal mammary epithelial, liver and kidney cells, showing a favorable safety window. PROTAC EZH2 Degrader-44 is an ideal tool molecule for exploring the mechanisms of targeted therapy for triple-negative breast cancer. (Pink: EZH2 ligand ; Blue: VHL ligand ; Black: linker).

PROTAC EZH2 Degrader-42 (compound 57) is an EZH2-targeting PROTAC degrader and antiproliferative agent. PROTAC EZH2 Degrader-42 induces cIAP-mediated ubiquitination and subsequent proteasomal degradation of EZH2. PROTAC EZH2 Degrader-42 can be used for the research of lymphoma. (Pink: Histone Methyltransferase ligand ; Blue: Aminopeptidase ligand ; Black: linker).

PROTAC EZH2 Degrader-41 is an EZH2-targeting PROTAC and cIAP E3 ubiquitin ligase recruiter. PROTAC EZH2 Degrader-41 induces EZH2 degradation via ubiquitination and proteasomal breakdown. PROTAC EZH2 Degrader-41 exerts antiproliferative effects in lymphoma cells. PROTAC EZH2 Degrader-41 can be used for the research of lymphoma. (Pink: Histone Methyltransferase ligand ; Blue: cIAP ligand ; Black: ).

PROTAC EZH2 Degrader-31(compound 69) is a PROTAC protein degrader targeting EZH2, with antiproliferative IC50 values of 3.63 μM in lSU-DHL-6 cells and 8.74 μM in HBL-1 cells. PROTAC EZH2 Degrader-31 can be used for the research of lymphoma. (Pink: EZH2 ligand ; Blue: MDM2 ligand ; Black: linker).

PROTAC EZH2 Degrader-17 (compound 52) is a PROTAC protein degrader targeting EZH2 with an antiproliferative IC50 of 18.32 μM in lymphoma cells. PROTAC EZH2 Degrader-17 exhibits antiproliferative activity against lymphoma cells. PROTAC EZH2 Degrader-17 can be used for the research of lymphoma. (Pink: Histone Methyltransferase ligand ; Blue: Cereblon ligand ; Black: linker).

PROTAC EGFR degrader 17 (Compound 35) is an EGFR PROTAC degrader with a DC50 value of 0.49 nM. PROTAC EGFR degrader 17 promotes the ubiquitination and degradation of EGFR. PROTAC EGFR degrader 17 can be used in research on various cancers, including non-small cell lung cancer. (Pink: EGFR ligand ; Blue: TNF Receptor ligand ; Black: linker).

PROTAC CDK9 degrader-12 is a selective CDK9 PROTAC degrader with a DC50 of 23 nM. PROTAC CDK9 degrader-12 induces proteasome-dependent degradation of CDK9, blocks CDK9-mediated HIV-1 transcriptional elongation, and reduces HIV-1 RNA synthesis. PROTAC CDK9 degrader-12 is applicable to research related to HIV-1 infection. (Pink: CDK9 ligand ; Blue: VHL ligand ; Black: linker).

PROTAC CDK2-pRb degrader-1 is an orally active PROTAC-class degrader of CDK2. PROTAC CDK2-pRb degrader-1 effectively inhibits the phosphorylation of retinoblastoma protein (Rb) at serine residues 807/811 by inducing ubiquitination and proteasomal degradation of CDK2. PROTAC CDK2-pRb degrader-1 exhibits significant activity against human cells (with EC50 values of 12 nM and 125 nM, respectively). In xenograft models, PROTAC CDK2-pRb degrader-1 effectively inhibits tumor growth and induces tumor stasis, making it suitable for research related to CCNE1-amplified cancers (such as ovarian cancer, gastric cancer, and breast cancer).

PROTAC BTK Degrader-4 (compound 15) is a potent PROTAC Bruton's tyrosine kinases (BTK) degrader (DC50 < 100 nM) with little immunomodulatory imide drug (IMiD) activity (DC50 = 0.345 μM, Dmax = 27.4%). PROTAC BTK Degrader-4 can be used for cancers, autoimmune diseases, and inflammatory diseases that are mediated by BTK. (Pink: Btk ligand ; Blue: Ligands for E3 Ligase and Cereblon E3 ligase ligand; Black: linker).

PROTAC BTK degrader-14 (compound 112) is a PROTAC protein degrader targeting BTK. PROTAC BTK degrader-14 can be used for the research of cancer.

PROTAC AAK1 Degard-1 (the fourth product on page 96) is an effective PROTAC AAK1 degrader that can be used in cancer research.

Propiomazine maleate is an orally active antihistamine agent. Propiomazine maleate is a potent prolactin (PRL) release stimulant, whose effect depends on the antagonism of the dopaminergic system and can inhibit the secretion of luteinizing hormone (LH). Propiomazine maleate is mainly used for anesthesia assistance, mental disorders and anxiety-induced sedation, and can also be used in research related to insomnia.

PRMT5-IN-54 (example 92a) is a protein arginine methyltransferase 5 (PRMT5) inhibitor. PRMT5-IN-54 can be used for the study of autoimmune diseases.

PRMT5 ligand 3 (Compound S19) is a PRMT5 ligand that can be used for the synthesis of PROTACs, such as RAPRMT5.

Pomalidomide-C9-Br is a synthesized E3 ligase ligand-linker conjugate that can be used to synthesize PROTAC EGFR degrader 15. PROTAC EGFR degrader 15 is a potent EGFR PROTAC degrader with anti-cancer activity.

Polθ-IN-9 is an orally active Polθ polymerase inhibitor (IC50 = 9.6 nM, Kd = 47.5 nM). Polθ-IN-9 shows remarkable selectivity with no inhibitory activity against other human DNA polymerases, including Pol α, Pol ε, Pol γ, Pol λ, and Pol μ. Polθ-IN-9 exhibits strong antiproliferative activity in DLD1 BRCA2 KO cells (IC50 = 2.9 μM), and high sensitivity to MDA-MB-436 cells (IC50 = 4.9 μM). Polθ-IN-9 increases DNA damage accumulation, induces γH2AX levels, and inhibits tumor growth in combination with Olaparib, in the MDA-MB-436 xenograft model. Polθ-IN-9 can be used for the research of homologous recombination (HR)-deficient cancers such as breast cancer.

PNU 101850 is an Eperezolid ester prodrug. PNU 101850 acquires antibacterial activity after conversion to the parent drug Eperezolid.

PMEG is a nuclear DNA polymerases α, δ, and ε inhibitor that causes DNA chain termination, inhibits DNA synthesis, induces cytotoxicity in dividing cells. PMEG is an acyclic nucleotide phosphonate that forms an active phosphorylated metabolite, PMEG diphosphate, within cells. PMEG has activity against leukemia and melanoma in rodent models. PMEG has poor cell permeability; its prodrug is Rabacfosadine (GS-9219). PMEG shows antiviral activity against against various DNA virus infections including murine cytomegalovirus (MCMV) and human cytomegalovirus (HCMV). PMEG can be used for the research of non-hodgkin's lymphoma[1][2].

PLX-4104 is an orally active BRD4 molecular glue degrader with a DC50 of 2 nM. PLX-4104 selectively promotes BRD4 degradation via DCAF11 recruitment, triggering ubiquitination and proteasomal breakdown. PLX-4104 inhibits cancer cell proliferation. PLX-4104 induces complete regression of AML xenograft tumors. PLX-4104 can be used for the research of acute myeloid leukemia.

PKMYT1-IN-11 (Example 1) is a PKMYT1 inhibitor with an IC50 of 4.49 nM. PKMYT1-IN-11 inhibits the proliferation of HCC1569 cells. When combined with Gemcitabine, PKMYT1-IN-11 shows a significant anti-tumor effect in the OVCAR3 xenograft mouse model. PKMYT1-IN-11 can be used for the study of various cancers such as breast cancer and ovarian cancer.

PKM2 agonist-1 (Compound D16) is a highly effective, allosteric PKM2 agonist with an AC50 value of 77 nM. PKM2 agonist-1 inhibits Ang II-induced smooth muscle cell phenotypic switching. PKM2 agonist-1 effectively prevents aortic dissection and results in reduced mortality.

PIN1 degrader-3 is a Pin1 (peptidyl-prolyl isomerase protein) (IC50 = 4.65 nM) degrader. PIN1 degrader-3 bound covalently to Pin1. PIN1 degrader-3-induced Pin1 degradation reduced cell viability, with EC50 values after 72 h of 8.4 μM in MIA PaCa-2 cells and 5.3 μM in KPC cell lines.PIN1 degrader-3 can destabilize Pin1 in vitro, causing its degradation in cells. PIN1 degrader-3 can be used for the study of pancreatic cancer.

PIM-IN-3 (Compound 50) is an orally active new anti-intestinal worm drug. PIM-IN-3 exhibits strong inhibitory activity in vitro, especially for whipworms (IC50 = 6.6 µM). PIM-IN-3 has low cytotoxicity. PIM-IN-3 can be used in the research of gastrointestinal nematode diseases.

PI3Kδ-IN-27 is an PI3Kδ inhibitor with an IC50 of 355.3 nM. PI3Kδ-IN-27 exhibits anti-SARS-CoV-2 activity. PI3Kδ-IN-27 can be used for the research of infection, such as COVID-19.

PI3Kα-IN-31 is an orally active and selective PI3Kα inhibitor. PI3Kα-IN-31 shows potent preference for mutant PI3Kα over wild-type PI3Kα. PI3Kα-IN-31 exerts antiproliferative effects in PI3Kα-mutant cancer cells. PI3Kα-IN-31 suppresses tumor growth in xenograft models. PI3Kα-IN-31 can be used for the research of breast cancer.

PI3Kα-IN-27 (Compound 50b) is an orally active PI3K-α inhibitor, with an IC50 of 40 nM. PI3Kα-IN-27 effectively inhibits PAK3, p110α, phospho-mTOR and phospho-ERK1/2. PI3Kα-IN-27 induces early Apoptosis. PI3Kα-IN-27 shows anticancer activity against pancreatic cancer, lung cancer, breast cancer.