RTX

Resiniferatoxin ((+)-Resiniferatoxin) is a highly potent synthetic TRPV1 agonist that inhibits the production of Th1 cytokines and has anti-inflammatory activity, reducing serum levels of IL-12, INF-γ, IL-1β, TNF-α, NO, and PGE.

RTx-161 is an allosteric Polθ polymerase inhibitor with an IC50 value of 4.1 nM. It selectively kills HR-deficient cancer cells and inhibits PARP inhibitor (PARPi) resistance across various genetic backgrounds, including HR-proficient cells. RTx-161 also induces apoptosis.

RTx-152 is an allosteric Polθ-pol inhibitor (IC50: 6.2 nM) that targets Polθ captured on DNA. It selectively kills cancer cells with homologous recombination (HR) defects and inhibits resistance to PARP inhibitors across various genetic backgrounds, including HR-proficient cells. Additionally, RTx-152 selectively eliminates BRCA2-deficient cells.

MRTX1133 is a KRAS G12D inhibitor (KD=0.2 pM) that is potent, selective, and non-covalent. MRTX1133 exhibits inhibitory activity against KRAS G12D-mutated tumors, but not against KRAS wild-type tumors.

MRTX-1719 is a potent and selective inhibitor of the PRMT5/MTA complex with an IC50 value of <10 nM against PRMT5/MTAMTAPDELSDMA cell lines.

MRTX-1257 is a selective, irreversible, and covalent inhibitor of KRAS G12C with an IC50 of 900 pM for KRAS-dependent ERK phosphorylation in H358 cells. MRTX-1257 demonstrated 31% bioavailability in the mouse, with free fraction exposures well above cellular potency, and 77% target engagement in a PK/PD experiment.

MRTX9768 hydrochloride is a potent, orally active PRMT5 inhibitor. MRTX9768 hydrochloride is a synthetic lethal-based inhibitor binding the PRMT5-MTA complex[1]. MRTX9768 inhibits SDMA and cell proliferation in HCT116 MTAP-del cells (SDMA IC50 3 nM; prolif. IC50 11 nM) with marked selectivity over HCT116 MTAP-WT cells (SDMA IC50 544 nM; prolif. IC50 861 nM)[1].MRTX9768 selectively targets MTAP/CDKN2A-deleted tumors[2][1]. In xenograft studies, oral administration of MRTX9768 demonstrates dose-dependent inhibition of SDMA in MTAP-del tumors, with less SDMA modulation observed in bone marrow[1]. [1]. Christopher R. Smith, et al. Abstract LB003: Fragment based discovery of MRTX9768, a synthetic lethal-based inhibitor designed to bind the PRMT5-MTA complex and selectively target MTAP/CDKN2A-deleted tumors. AACR Annual Meeting 2021; April 10-15, 2021 and May 17-21, 2021; Philadelphia, PA.[2]. Yingqing Chen, et al. Targeting protein arginine methyltransferase 5 in cancers: Roles, inhibitors and mechanisms. Biomed Pharmacother. 2021 Oct 4;144:112252.

MRTX1133 is a highly selective, first-in-class inhibitor of KRAS G12D. MRTX1133 targets the KRAS G12D protein in both active and inactive states. MRTX1133 selectively inhibits KRAS G12D mutant, but not KRAS wild-type, tumor cells[1][2]. MRTX1133 demonstrates dose-dependent inhibition of the KRAS pathway tumor regression in G12D mutant tumor models[2]. [1]. Xiaolun Wang, et al.Kras g12d inhibitors.WO2021041671A1.[2]. KRAS G12D Inhibitor: MRTX1133. [(accessed on 22 April 2021)];2021 Available online.

MRTX849 analog 24, an alkyne-containing click probe analogue of the MRTX849 inhibitor for KRAS G12C, is designed for studying MRTX849 functionality.

MRTX849 acid, a derivative of MRTX849, is employed in the synthesis of PROTAC LC-2. LC-2, a potent and pioneering PROTAC, exhibits the ability to efficiently degrade endogenous KRAS G12C with DC50 values ranging between 0.25 and 0.76 μM.

MRTX849 ethoxypropanoic acid is a compound that contains a ligand for KRAS G12C and a PROTAC linker. It is commonly employed in the synthesis of PROTAC LC-2, which is a highly effective and innovative PROTAC. LC-2 has been proven to degrade endogenous KRAS G12C with remarkable potency, exhibiting DC50 values ranging from 0.25 to 0.76 μM.

(S)-MRTX-1719 is the S-enantiomer of Navlimetostat and acts as a PRMT5/MTA complex inhibitor with an IC50 value of 7070 nM, enabling selective modulation of arginine methylation, epigenetic regulation, and transcriptional control, (S)-MRTX-1719 is widely applied in cancer epigenetics research to investigate PRMT5-dependent tumor growth and therapeutic vulnerabilities.

MRTX-EX185 is an effective inhibitor of GDP-loaded KRAS and KRAS (G12D) with an IC50=90 nM for KRAS (G12D). MRTX-EX185 is also capable of binding GDP-loaded HRAS.

GrTx1, a peptide toxin derived from Grammostola rosea spider venom, selectively inhibits sodium channels Nav1.1, Nav1.2, Nav1.3, Nav1.4, Nav1.6, and Nav1.7, with IC50 values of 0.63 µM, 0.23 µM, 0.77 µM, 1.29 µM, 0.63 µM, and 0.37 µM, respectively [2]. This compound has applications in neurological disease research [1].

π-TRTX-Hm3a, a 37-amino acid peptide derived from the venom of the Togo starburst tarantula (Heteroscodra maculata), selectively inhibits the acid-sensing ion channel 1a (ASIC1a) in a pH-dependent manner, with an inhibitory concentration half-max (IC50) of 1-2 nM, and also potentiates the activity of acid-sensing ion channel 1b (ASIC1b) with an effective concentration half-max (EC50) of 46.5 nM [1].

μ-TRTX-Hd1a, a spider venom-derived compound, selectively inhibits the human NaV 1.7 channel by functioning as a gating modifier, interacting with the S3b-S4 paddle motif within domain II of the channel [1].

MRTX-9768 is a synthetic lethal-based inhibitor designed to bind the PRMT5-MTA complex and selectively target MTAP/CDKN2A-deleted tumors.

MRTX0902 is an effective and high selective inhibitor of SOS1 with an IC50 of 46 nM and a Ki of 2 nM.

Adagrasib (MRTX849) is an orally active and selective covalent inhibitor of KRAS G12C. Adagrasib binds to the GDP state of the inactive conformation of KRAS G12C and inhibits KRAS and its downstream signaling. Adagrasib exhibits inhibitory activity against KRAS G12C mutant tumors.

ProTx-III, a spider venom peptide derived from the Peruvian green velvet tarantula, functions as a selective and potent inhibitor of the voltage-gated sodium channel Na v 1.7, exhibiting an IC 50 of 2.1 nM. Characterized by its inhibitor cystine knot motif (ICK), ProTx-III can attenuate the pain response and is applicable in research on chronic pain, epilepsy, and arrhythmia [1].

Phlo1b (μ-TrTx-Phlo1b), a 35-amino acid peptide toxin, selectively inhibits Nav1.7 channels with minimal inhibition of Nav1.2 and Nav1.5 [1].

Phlo1a (μ-TrTx-Phlo1a), a 35-amino acid peptide toxin, demonstrates a weak inhibitory effect on Nav1.2 and Nav1.5 channels [1]. Meanwhile, Phlo1b acts as a selective inhibitor of the Nav1.7 channel.

Pe1b (μ-TrTx-Pe1b) is a selective NaV1.7 channel inhibitor with an inhibitory concentration 50 (IC50) value of 167 nanomolar (nM) [1].

Ceratotoxin-2 (CcoTx2) is a voltage-gated sodium channel inhibitor with half maximal inhibitory concentrations (IC50) of 8 nM for Na v 1.2/β 1 and 88 nM for Na v 1.3/β 1 [1].