h-NTPDase8-IN-1 is a specific aminosulfonylbenzamide inhibitor of h-NTPDases8 (IC 50 = 0.28 ± 0.07 μM). h-NTPDase8-IN-1 can be used to study diseases brought about by aberrant h -NTPDase expression.

DB0614 (Example 21) is a bifunctional compound designed for the targeted degradation of kinases, effectively breaking down a wide array of kinases including AAK1, AURKA, BMP2K, CAMKK1, CDK16, CML, CDK6, EIF2AK2, FER, GAK, LCK, LIMK2, MAP3KH, MAPK8, MAPK9, NEK9, PLK4, PTK2B, SIK2, STK17A, STK17B, ULK1, ULK3, and WEE1. This compound has potential applications in the research of diseases or disorders caused by aberrant kinase activity [1].

ARI-1 is a receptor tyrosine kinase-like orphan receptor 1 (ROR1) inhibitor that binds to ROR1's extracellular Frizzled domain, effectively inhibiting aberrant ROR1 expression linked to non-small cell lung cancer (NSCLC) and EGFR-TKI-induced drug resistance. It modulates PI3K/AKT/mTOR signaling pathways in a ROR1-dependent manner and demonstrates potent inhibition of NSCLC cell proliferation and migration, exhibiting antitumor activity in vivo [1].

CLR01 is a molecular tweezer. CLR01 reduces aggregated, pathologic, and seeding-competent α-synuclein in experimental multiple system atrophy. CLR01 inhibits aberrant superoxide dismutase 1 (SOD1) self-assembly in vitro and in the G93A-SOD1 mouse model of ALS. CLR01 inhibits Ebola and Zika virus infection. CLR01 Stabilizes a Disordered Protein-Protein Interface. CLR01, Modulates Aggregation of the Mutant p53 DNA Binding Domain and Inhibits Its Toxicity.

DB1113 (Example 24) is a bifunctional compound designed for the targeted degradation of various kinases. It effectively degrades a range of kinases, including ABL1, ABL2, BLK, CDK11B, CDK4, CSK, EPHA3, FER, GAK, LIMK1, MAP3K20, MAP4K1, MAP4K2, MAP4K3, MAP4K5, MAPK14, MAPK7, MAPK8, MAPK9, MAPKAPK2, MAPKAPK3, NLK, PDIK1L, PTK2B, RIPK1, RPS6KA1, RPS6KA3, SIK2, SIK3, STK35, TNK2, and ULK1. This capability positions DB1113 as a valuable tool for research into diseases or disorders associated with aberrant kinase activity [1].

cis-4-Br-2,5-F2-PCPA (S1024) inhibits LSD1 and LSD2 with Ki values of 94 nM and 8.4 μM, respectively. There is aberrant expression of LSD1 in cancer stem cells, cis-4-Br-2,5-F2-PCPA inhibits LSD1 cell proliferation and by increasing the level of dimethylated histone H3 at K4 (H3K4) in CCRF-CEM cells [1].

TNO155 is a protein tyrosine phosphatase (PTP) non-receptor type 11 (SHP2; src homology region 2 domain phosphatase; PTPN11) inhibitor(IC50 : 0.011 µM),with potential antineoplastic activity.

Indibulin (D 24851) is a synthetic small molecule with antimitotic and potential antineoplastic activities.Indibulin an orally applicable inhibitor of tubulin assembly, shows potent anticancer activity with a minimal neurotoxicity. Indibulin reduces inter-kinetochoric tension, produces aberrant spindles, activates mitotic checkpoint proteins Mad2 and BubR1, and induces mitotic arrest and apoptosis.

AZD-9574 is a selective inhibitor of PARP1 at the sites of SSBs. AZD-9574 exhibits anti-cancer activities and can be used in studies about HRD+ breast cancer and advanced solid malignancies.

NDI-034858 (TAK-279) is a tyrosine kinase 2 (TYK2) inhibitor (Kd<200 pM) that targets the JH2 structural domain of Tyk2 for the treatment of autoimmune diseases caused by aberrant expression of IL12 and IL23.

RO5068760 , a substituted hydantoin, is a potent, highly selective, non-adenosine triphosphate (ATP)-competitive MEK1/2 inhibitors. RO5068760 shows significant efficacy in a broad spectrum of tumors with aberrant mitogen-activated protein kinase pathway activation. In vitro, RO5068760 demonstrates MEK1 kinase inhibitory activity with an IC50 of 0.025 μM in a cRaf/MEK/ERK cascade assay RO5068760 showed superior efficacy in tumors harboring B-RafV600E mutation.

Tie2 Inhibitor 7 blocks Tie2 kinase activity with a Ki value of 1.3 μM.. It has been shown to inhibit angiopoietin 1-induced Tie2 autophosphorylation and downstream signaling with an IC50 value of 0.3 μM. This compound can prevent endothelial cell tube formation and aberrant vessel growth in a rat model of Matrigel-induced choroidal neovascularization.

RO4927350 is a potent and highly selective non-ATP-competitive MEK1/2 inhibitor. RO4927350 selectively blocks the MAPK pathway signaling both in vitro and in vivo, which results in significant antitumor efficacy in a broad spectrum of tumor models. RO4927350 inhibits not only ERK1/2 but also MEK1/2 phosphorylation. In cancer cells, high basal levels of phospho-MEK1/2 rather than phospho-ERK1/2 seem to correlate with greater sensitivity to RO4927350. Furthermore, RO4927350 prevents a feedback increase in MEK phosphorylation, which has been observed with other MEK inhibitors. RO4927350 represents a novel therapeutic modality in cancers with aberrant MAPK pathway activation.

DUB-IN-7 (compound 43), a deubiquitinating enzyme (DUB) inhibitor, has utility in researching diseases driven by aberrant JAK2 activity, including leukemia [1].

(S)-Cdc7-IN-18, a potent CDC7 inhibitor, effectively impedes the overactivation of MCM2, a crucial tumor cell marker, induced by huCdc7 overexpression. Consequently, it inhibits the aberrant proliferation of tumor cells. This compound, exhibits promise for cancer disease research [1].

DAT-230 is a promising microtubule inhibitor that has great potential for the treatment of fibrosarcoma in vitro and in vivo. DAT-230 exhibited potent anti-proliferative activity against various cancer cells. DAT-230 -treatment in HT-1080 cells resulted in microtubule de-polymerization and G2/M phase arrest preceding apoptosis. Phosphor-cdc2 (thr14/tyr15) reduction, cyclin B1 accumulation and aberrant spindles denoted the cyclin B1-cdc2 complex active and M phase arrest in HT-1080 cells treated with DAT-230. Apoptosis induced by DAT-230 was related with the activation of caspase-9, caspase-3 and PARP cleavage, which were at the downstream of mitochondria.

Tirabrutinib (GS-4059) (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.

(R)-MLT-985 (compound 11) is a potent inhibitor of MALT1 protease (IC50: 3 nM). (R)-MLT-985 has an IC50 value of 20 nM for MALT1-dependent IL-2 in Jurkat cells.(R)-MLT-985 inhibits growth and aberrant CARD11/BCL10/MALT1 complex signaling in ABC-DLBCL cells.

AMG-337 monohydrate is a highly selective small molecule MET inhibitor. Aberrant hepatocyte growth factor (HGF)/MET signaling has been implicated in hepatocarcinogenesis, suggesting that MET may serve as an attractive therapeutic target in hepatocellular carcinoma.

LSD1/2-IN-3 is a selective inhibitor of lysine-specific demethylase 1 ( LSD1 ) with a Ki value of 11 nM rather than 7 μM for LSD2. There is aberrant expression of LSD1 in tumor stem cells, LSD1/2-IN-1 inhibits LSD1 cell proliferation [1].

SSE15206 is a microtubule polymerization inhibitor that overcomes multidrug resistance. Causes aberrant mitosis resulting in G2/M arrest due to incomplete spindle formation in cancer cells.

PKR-IN-C51 is an inhibitor of protein kinase R. It acts by correcting the aberrant splicing of MBNL1-dependent pre-mRNAs in DM1 cells without affecting the splicing pattern in normal non-DM1 cells.

BMS-984923 is an orally available and blood-brain barrier permeable mGluR5 silencing allosteric modulator that inhibits β-amyloid oligomer-induced aberrant synaptic signaling, and can be used to study Alzheimer's disease.

AUH-6-96 is an inhibitor of JAK/STAT signaling, inhibiting both constitutive and interleukin-6-induced STAT3 phosphorylation, selectively affecting cell viability only of cancer cells harboring aberrant JAK/STAT signaling.

Rogaratinib (BAY1163877) is an aberrant inhibitor of fibroblast growth factor receptor (FGFR). Rogaratinib is as an orally available, selective and potent inhibitor of FGFR-1, -2 and -3 kinase activity.

4SC-207 is a novel microtubule inhibitor , which shows strong anti-proliferative activity in a large panel of tumor cell lines with an average GI50 of 11 nM. In particular, 4SC-207 is active in multi-drug resistant cell lines, such as HCT-15 and ACHN, suggesting that it is a poor substrate for drug efflux pumps. 4SC-207 inhibits microtubule growth in vitro and in vivo and promotes, in a dose dependent manner, a mitotic delay/arrest, followed by apoptosis or aberrant divisions due to chromosome alignment defects and formation of multi-polar spindles. Furthermore, preliminary data from preclinical studies suggest low propensity towards bone marrow toxicities at concentrations that inhibit tumor growth in paclitaxel-resistant xenograft models. 4SC-207 may be a potential anti-cancer agent.