patient-derived

FGTI-2734 is a dual farnesyl transferase (FT) and geranylgeranyl transferase-1 (GGT-1) inhibitor, exhibiting IC50 values of 250 nM and 520 nM for FT and GGT-1, respectively. It effectively prevents the membrane localization of KRAS, addressing the issue of KRAS resistance and inhibiting the growth of mutant KRAS patient-derived pancreatic tumors.

PF-9363 (CTX-3648) is a potent and high selective KAT6A/KAT6B inhibitor. PF-9363 can be used for the research of cancer.

IACS-010759 hydrochloride is an orally potent and selective OXPHOS inhibitor that inhibits proliferation and induces apoptosis in OXPHOS-dependent brain cancer and acute myeloid leukaemia models for the study of relapsed/refractory AML and advanced solid tumours.

FGTI-2734 mesylate, a RAS C-terminal mimetic compound with dual farnesyl transferase (FT) and geranylgeranyl transferase-1 (GGT) inhibitory activities (IC50s of 250 nM and 520 nM for FT and GGT, respectively), mitigates KRAS resistance by preventing its membrane localization, effectively impeding mutant KRAS patient-derived pancreatic tumors.

MS40 is a WDR5 PROTAC that selectively degrades WDR5 and serves as a novel degrader for immune-modulating compounds (IMiDs), including the new substrates CRBN and Ikaros zinc finger (IKZF) transcription factors IKZF1 and IKZF3. MS40 facilitates the degradation of WDR5, resulting in the dissociation of the MLL/KMT2A complex from chromatin, thereby reducing H3K4me2 levels. In vitro, MS40 inhibits the growth of primary leukemia patient cells, and in vivo, it suppresses the expansion of patient-derived xenografts.

Mal-N(Me)-C6-N(Me)-PNU-159682 (Compound 27) is an active molecular conjugate used in antibody-drug conjugates (ADCs), consisting of the ADC linker Mal-N(Me)-C6-N(Me) and the potent cytotoxin PNU-159682. This compound selectively delivers its payload to cells expressing CD46 and releases PNU-159682 through cathepsin B cleavage of the linker, inducing DNA damage and apoptosis. Mal-N(Me)-C6-N(Me)-PNU-159682 has demonstrated sustained tumor regression in patient-derived xenograft (PDX) models of non-small cell lung cancer (NSCLC) and colorectal cancer (CRC).

TH287 is a selective MTH1 inhibitor(IC50 : 0.8 nM). It causees incorporation of oxidized dNTPs in cancer cells, leading to DNA damage, cytotoxicity and therapeutic responses in patient-derived mouse xenografts.

HEMTACWEE1degrader-1 is a WEE1-targeting heterobifunctional chimeric degrader (HEMTAC) facilitated by HSP90, exhibiting an HSP90 enzyme inhibitory activity with an IC50 of 16.76 nM. It enhances the ubiquitination and subsequent degradation of WEE1, effectively blocking the G2/M cell cycle transition. This compound shows anticancer properties in patient-derived xenograft (PDX) models of acute myeloid leukemia (AML). HEMTACWEE1degrader-1 is utilized in AML research.

EGFR-IN-91 (compound 9) is an orally active EGFR inhibitor capable of crossing the blood-brain barrier. It effectively inhibits EGFRL858R/C797S and EGFRexon 19del/C797S, leading to tumor regression in patient-derived xenograft (PDX) mouse models. EGFR-IN-91 shows potential for inhibiting locally advanced and metastatic non-small cell lung cancer (NSCLC) driven by EGFR mutations.

VT02956 is an inhibitor of LATS with an IC50 of 0.76 nM for LATS1 and 0.52 nM for LATS2. It targets the Hippo signaling pathway and suppresses the growth of ER+ breast cancer cell lines and patient-derived tumor organoids, as well as the expression of ESR1.

Antitumor agent-139 (compound 9b) is a gold (I) complex targeting liver and mitochondria, capable of generating reactive oxygen species (ROS) and facilitating DNA excretion. It inhibits tumor growth in patient-derived liver cancer xenograft models.

MXC-017 is an apoptosis inducer capable of crossing the blood-brain barrier, specifically targeting glioma stem cells (GSCs). It effectively prevents the formation of radiation-induced GSCs while promoting G0/G1 cell cycle arrest and apoptosis. With minimal off-target effects, MXC-017 exhibits no significant cytotoxicity even at concentrations up to 10 µM. Additionally, it significantly extends the median survival in patient-derived orthotopic xenograft (PDOX) glioblastoma (GBM) mouse models when used in conjunction with radiation therapy.

GPX4-AUTAC is an autophagy-mediated degrader (AUTAC) targeting GPX4. It consists of the inhibitor ML162-yne, a degradation tag FBnG, and a glycol linker. GPX4-AUTAC facilitates the ubiquitination of GPX4 by the E3 ligase TRAF6 and enhances its interaction with GPX4 and p62, leading to selective autophagy-dependent degradation of GPX4. This compound significantly induces ferroptosis and demonstrates potent anticancer activity in breast cancer cells, patient-derived organoids (PDOs), and MDA-MB-231 tumor xenograft mouse models. It shows strong synergy when used in combination with Sulfasalazine (SAS) or chemotherapy drugs (Paclitaxel or Cisplatin).

Potent and selective BTK Degrader (IC50 = 5.1 nM); degrades BTK in a proteasome- and CRBN-dependent manner. Suppresses BTK signaling and proliferation in mantle cell lymphoma (MCL) cells by degrading BTK, IKFZ1, and IKFZ3 (3 validated targets in B-cell malignancies). Also degrades Ibrutinib (Cat. No. 6813) -resistant C481S-BTK mutant cancer cells. Exhibits no binding against a panel of 468 kinases at 1 μM. Reduces tumor burden and extends survival in lymphoma patient-derived xenograft models.

Promotes proteasomal degradation of Miro1 (mitochondrial Rho GTPase 1). Reduces Miro1 levels in fibroblasts from Parkinson's disease (PD) patients (IC50 = 7.8 μM). Exhibits no significant effect on related outer mitochondrial membrane protein Mitofusin. Reduces stress-induced degeneration of dopaminergic neurons derived from PD patient iPSCs. Rescues age-dependent neuronal loss and prolongs lifespan in fly PD models.

CAY10722 is an inhibitor of sirtuin 3 (SIRT3), a class III HDAC (71% inhibition at 200 μM). SIRT3 is involved in modulating metabolic homeostasis as a NAD+-dependent protein deacetylase in the mitochondria. SIRT3 functions as either an oncogene or tumor suppressor, depending on cancer cell type. High SIRT3 expression in patient-derived esophageal cancer tissues is associated with shorter survival and, in mice, downregulation leads to a lower tumor load. In contrast, low SIRT3 expression in patient-derived breast cancer cells is correlated with shorter survival.

Darinaparsin is a dimethylated arsenic linked to glutathione. It is cytotoxic to DU145, LNCaP, and PC3 prostate cancer cells (IC50s = 5-10 µM) and patient-derived primary prostate cancer cells (IC50s = 2.5-20 µM), as well as Jurkat T cell lymphoma and L540 Hodgkin lymphoma cells (IC50s = 2.7 and 1.3 µM, respectively). [1][2] It decreases the tumor-initiating subpopulation in DU145 and PC3 cells and halts the cell cycle in the G2/M phase. Darinaparsin decreases transcription of Gli-2, a transcription factor that mediates Sonic hedgehog signaling, when used at a concentration of 1.5 but not 3 µM. It decreases SHP1 phosphatase activity and increases ERK phosphorylation. [2] Darinaparsin reduces tumor growth in DU145 and PC3 prostate cancer mouse xenograft models when administered at a dose of 100 mg/kg every other day.[1]

5-Chlorouracil is a chlorinated derivative of the pyrimidine nucleoside base uracil . In vivo, it is converted into chlorodeoxyuridine, which is mutagenic and genotoxic.1 Uracil is chlorinated at the 5 position in a cell-free myeloperoxidase, peroxide, and chloride system in which hypochlorous acid is formed.2 5-Chlorouracil has been found in human neutrophils stimulated with phorbol 12-myristate 13-acetate in vitro and in inflammatory human exudate isolated from sites of superficial infection. Levels of 5-chlorouracil are increased in exudate isolated from the site of inflammation in a rat model of carrageenan-induced inflammation and in patient-derived human atherosclerotic aortic tissue.3,4References 5-Chlorouracil is a chlorinated derivative of the pyrimidine nucleoside base uracil . In vivo, it is converted into chlorodeoxyuridine, which is mutagenic and genotoxic.1 Uracil is chlorinated at the 5 position in a cell-free myeloperoxidase, peroxide, and chloride system in which hypochlorous acid is formed.2 5-Chlorouracil has been found in human neutrophils stimulated with phorbol 12-myristate 13-acetate in vitro and in inflammatory human exudate isolated from sites of superficial infection. Levels of 5-chlorouracil are increased in exudate isolated from the site of inflammation in a rat model of carrageenan-induced inflammation and in patient-derived human atherosclerotic aortic tissue.3,4 References

Selective peptide-based β-catenin Degrader. Comprises a β-catenin-targeted stapled peptide, xStAx, linked to a VHL-binding peptide. Reduces β-catenin levels in HEK293T cells and colorectal cancer cell lines. Selectively degrades β-catenin over other Wnt signaling pathway components. Inhibits tumor growth in APCmin/+ mice, with constitutively active Wnt signaling, and reduces survival of patient-derived colorectal cancer cell organoids.

1,2-Dipalmitoyl-sn-glycero-3-PE-N-(cap biotin) is a biotinylated phospholipid. It has been used in PEGylated polyamidoamine-dendrimer-conjugated supported lipid bilayers (SLB) to isolate circulating tumor cells and tumor cell microembolis from patient-derived blood by antibody-coated microfluidics. [1] It has also been used as a component of SLBs to detect protein-ligand binding with ortho-conjugated Texas Red DHPE. [2] In addition, 1,2-dipalmitoyl-sn-glycero-3-PE-N-(cap biotin) has been used in SLBs partitioned into nanowells to create DNA curtains, which can be used as a high-throughput tool for detection of protein-DNA interactions at the single molecule level.[3]

ALDH3A1-IN-1 (Compound 18) is a potent ALDH3A1 inhibitor with an IC 50 of 1.61 μM. It is more effective than DEAB against patient-derived primary prostate tumor epithelial cells, both as a single agent and in combination with docetaxel [1].

DS89002333 is a potent, orally active PRKACA inhibitor (IC50: 0.3 nM).DS89002333 has shown good antitumor effects in a patient-derived xenograft model of FL-HCC expressing a DNAJB1-PRKACA fusion gene.DS89002333 can be used to study fibrotic hepatocellular carcinoma ( FL-HCC).

TG-693 is an orally active CLK1 (CDC2-like kinase 1) inhibitor that promotes exon 31 skipping of the dystrophin gene mutation in vivo and inhibits CLK1 substrate phosphorylation, suitable for studying Duchenne muscular dystrophy (DMD).

L-778123 is an inhibitor of FPTase and GGPTase-I, which was developed in part because it can completely inhibit Ki-Ras prenylation. The combination of L-778,123 and radiotherapy at dose level 1 showed acceptable toxicity in patients with locally advanced pancreatic cancer. Radiosensitization of a patient-derived pancreatic cancer cell line was observed.