knockout

SW033291 is a small-molecule inhibitor of 15-PGDH (Ki=0.1 nM) that increases prostaglandin PGE2 levels in bone marrow and other tissues.

iFSP1, a potent, selective, and glutathione-independent ferroptosis suppressor protein 1 (FSP1) (AIFM2) inhibitor with an EC50 of 103 nM, sensitizes diverse human cancer cell lines to ferroptosis inducers like (1S,3R)-RSL3. It uniquely triggers ferroptosis in GPX4-knockout cells overexpressing FSP1.

MK-1064 (Urokinase inhibitor 1) is a selective orexin 2 receptor antagonist (2-SORA).

Tamoxifen is an orally active selective estrogen receptor modulator (SERM) that acts as an estrogen antagonist in breast cells and an agonist in bone, liver, and uterine cells. It can be used to induce gene knockout and liver injury models in mice, and also exhibits multiple biological activities, including activation of Hsp90, induction of autophagy and apoptosis, and inhibition of EBOV and MARV viral infections.

Tamoxifen Citrate is an orally active selective estrogen receptor modulator (SERM) that blocks estrogen activity in breast cells while activating estrogen signaling in cells such as those of the bone, liver, and uterus. As an Hsp90 activator, it enhances the ATPase activity of the Hsp90 chaperone complex, induces autophagy and apoptosis, and can be used to generate gene knockout models in CreER(T2) transgenic mice as well as liver injury models.

Iso-SLR 080811 is an isomer of SLR 080811, suitable for relevant research in the life sciences. SLR080811 is a selective SphK2 inhibitor (Ki=1.3 μM) that elevates blood S1P levels in wild-type mice, reduces S1P levels in sphk1 knockout mice, and leaves S1P levels unchanged in SphK2 knockout mice.

24-Norursodeoxycholic acid (nor-UDCA) is a side chain-shortened C23 homolog of UDCA.It has shown potent anti-inflammatory, anti-cholestatic, and anti-fibrotic properties.It is a Ursodeoxycholic Acid derivative. It is superior to Ursodeoxycholic acid in the treatment of sclerosing cholangitis in Mdr2 (Abcb4) knockout mice

PRDX1-IN-3 (SOMCL-19-048) is a PRDX1 covalent inhibitor with anti-colorectal cancer activity. PRDX1-IN-3 can effectively inhibit the proliferation of colorectal cancer cells and significantly reduce the anti-tumor effect on colorectal cancer nude mice carrying PRDX1 gene knockout. PRDX1-IN-3 can also upregulate downstream genes of the p53 signaling pathway and exert anti-cancer effects.

LH1513 is a dioxalate salt derivative of l-lysine that inhibits CaOx crystallization more effectively than citrate and pyruvate. It shows potential preventive activity in hyperoxaluria models and effectively prevents urinary CaOx crystal formation in Agxt knockout mice. AGXT-1 is a mitochondrial protein involved in metabolic processes.

TFE-IDAtp1-LinA is an efficient amphiphilic carrier that contains a trifluoroethyl imino diacetic acid analogue with Stp. It forms nanoparticles with Cas9 RNP/ssDNA, facilitating the knockout of enhanced green fluorescent protein, with an ED50 of 0.38 nM Cas9/sgRNA ribonucleoprotein (RNP).

FMP-API-1 is an inhibitor of the A-kinase anchoring protein (AKAP)-PKA interaction. It binds to the allosteric site of the PKAR subunit, enhancing the activity of PKA and AQP2 in PKA knockout cell lines of the renal cortex collecting duct (mpkCCD cells). FMP-API-1 holds potential for studying nephrogenic diabetes insipidus (NDI).

Hypoxystat increases the affinity of hemoglobin for oxygen, thereby reducing the release of oxygen to tissues and inducing tissue hypoxia. [Hypoxystat] can alleviate mitochondrial disorder Leigh syndrome in Ndufs4 gene knockout mouse models. Hypoxystat is orally active.

TDI-012804 is a TNKS2 inhibitor that selectively inhibits endogenous TNKS2 protein within cells. It enhances the expression of AXIN1 protein in Tnks1 heterozygous (Tnks1HET) and knockout (Tnks1KO) cells. TDI-012804 suppresses the proliferation of ApcQ1405X/Tnks1KO organoids with an EC50 of 59.1 nM and exhibits selective toxicity towards Tnks1KO AKP-G12D and AKP-G13D organoids.

uPSEM792 is a pharmacologically selective agonist molecule (PSEM) for PSAM4-GlyR, with an affinity Ki of 0.7 nM. It acts as a substrate for efflux transporters in both wild-type mice brains and in P-gp and BCRP double knockout mice. Additionally, uPSEM792 may serve as a lead compound in the development of PET radioligands for PSAM4-GlyR.

GAT2711 is a full agonist of α9nAChR, with an EC50 of 230 nM. It exhibits 340 times greater selectivity for α9 over α7nAChR. In THP-1 cells, GAT2711 inhibits ATP-induced IL-1β release. Additionally, GAT2711 retains full analgesic activity in α7nAChR knockout mice.

SB-T-101141 is a novel taxane drug effective in inducing atypical ferroptosis, thereby overcoming resistance of breast cancer to Paclitaxel. It promotes the generation of iron ions, ferrous ions, and reactive oxygen species (ROS). SB-T-101141 stably binds to KHSRP, inhibiting the expression of the iron-dependent CISD1 related to iron homeostasis. It synergistically enhances the activation of the iron-dependent JNK and PERK pathways through KHSRP. SB-T-101141 inhibits breast tumor growth in MCF-7(PR)/MDA-MB-231(PR) or KHSRP knockout MCF-7 xenograft mouse models.

MP1202 is a dual agonist for MOR and KOR, with EC50 values of 0.32 μM for mMOR-1 and 0.13 μM for mKOR-1. It exhibits functional selectivity by reducing β-arrestin1/2 recruitment in hMOR and hKOR while significantly activating G protein and Gα subtypes. In opioid receptor subtype knockout mouse models, MP1202 demonstrates potent antinociceptive effects without typical opioid side effects, albeit it induces conditioned place preference and aversion behaviors, indicating potential for analgesic research.

LY-465608, a PPAR Agonist, inhibits macrophage activation and atherosclerosis in apolipoprotein E knockout mice.

Potent and selective p38α and p38β degrader (DC50 < 50 nM). Displays no significant degradation of p38γ, p38δ, JNK1/2 or ERK1/2. Inhibits phosphorylation of MK2 in UV-treated cancer cells and LPS-stimulated bone marrow-derived macrophages (BMDM). Exhibits similar effect to p38α gene knockout in BBL358 cells. Active in vivo.

GLP-1 amide is a peptide hormone cleaved from proglucagon in the pancreas.1,2 Mice lacking the glucagon receptor (Gcgr-/-) have approximately nine-fold higher levels of total GLP-1 amide, including GLP-1 (1-36) amide and truncated GLP-1 (7-36) amide , in pancreatic tissue compared to wild-type mice.2References1. Schjoldager, B.T., Mortensen, P.E., Christiansen, J., et al. GLP-1 (glucagon-like peptide 1) and truncated GLP-1, fragments of human proglucagon, inhibit gastric acid secretion in humans. Dig. Dis. Sci. 34(5), 703-708 (1989).2. Gelling, R.W., Du, X.Q., Dichmann, D.S., et al. Lower blood glucose, hyperglucagonemia, and pancreatic α cell hyperplasia in glucagon receptor knockout mice. Proc. Natl. Acad. Sci. U.S.A. 100(3), 1438-1443 (2003). GLP-1 amide is a peptide hormone cleaved from proglucagon in the pancreas.1,2 Mice lacking the glucagon receptor (Gcgr-/-) have approximately nine-fold higher levels of total GLP-1 amide, including GLP-1 (1-36) amide and truncated GLP-1 (7-36) amide , in pancreatic tissue compared to wild-type mice.2 References1. Schjoldager, B.T., Mortensen, P.E., Christiansen, J., et al. GLP-1 (glucagon-like peptide 1) and truncated GLP-1, fragments of human proglucagon, inhibit gastric acid secretion in humans. Dig. Dis. Sci. 34(5), 703-708 (1989).2. Gelling, R.W., Du, X.Q., Dichmann, D.S., et al. Lower blood glucose, hyperglucagonemia, and pancreatic α cell hyperplasia in glucagon receptor knockout mice. Proc. Natl. Acad. Sci. U.S.A. 100(3), 1438-1443 (2003).

CAY10748 is an agonist of stimulator of interferon genes (STING; IC50= 0.3794 μM in a competition binding assay).1It activates STING in STING-expressing, but not STING knockout, THP-1 cells (EC50s = 0.287 and >100 μM, respectively, in a reporter assay). It induces phosphorylation of STING at the serine in position 366, as well as phosphorylation of TBK1 and IFN regulatory factor 3 (IRF3), indicating activation of the STING-TBK1-IRF3 signaling pathway. CAY10748 increases the secretion of IFN-β and the levels of chemokine (C-X-C motif) ligand 10 (CXCL10), and IL-6 in peripheral blood mononuclear cells (PBMCs) when used at a concentration of 10 μM. It also reduces tumor growth in a CT26 murine colon cancer model when administered at a dose of 0.15, but not 1.5, mg/kg. 1.Xi, Q., Wang, M., Jia, W., et al.Design, synthesis, and biological evaluation of amidobenzimidazole derivatives as stimulator of interferon genes (STING) receptor agonistsJ. Med. Chem.63(1)260-282(2019)

Deltorphin II is a peptide agonist of δ2-opioid receptors.1,2It is selective for δ-opioid receptors over μ- and κ-opioid receptors in radioligand bindings assays (Kis = 0.0033, >1, and >1 μM, respectively) and induces [35S]GTPγS binding in mouse brain membrane preparations (EC50= 0.034 μM). Deltorphin II (0.12 mg/kg) decreases the infarction zone:risk zone ratio in a rat model of myocardial ischemia-reperfusion injury induced by coronary occlusion, an effect that can be reversed by the δ2-opioid receptor antagonist naltriben but not the δ1-opioid receptor antagonist BNTX.3Intrathecal administration of deltorphin II (15 μg/animal) increases latency to withdraw in the paw pressure and tail-flick tests in rats.4 1.Raynor, K., Kong, H., Chen, Y., et al.Pharmacological characterization of the cloned κ-, δ-, and μ-opioid receptorsMol. Pharm.45(2)330-334(1994) 2.Scherrer, G., Befort, K., Contet, C., et al.The delta agonists DPDPE and deltorphin II recruit predominantly mu receptors to produce thermal analgesia: A parallel study of mu, delta and combinatorial opioid receptor knockout miceEur. J. Neurosci.19(8)2239-2248(2004) 3.Maslov, L.N., Barzakh, E.I., Krylatov, A.V., et al.Opioid peptide deltorphin II simulates the cardioprotective effect of ischemic preconditioning: role of δ2-opioid receptors, protein kinase C, and KATP channelsBull. Exp. Biol. Med.149(5)591-593(2010) 4.Labuz, D., Toth, G., Machelska, H., et al.Antinociceptive effects of isoleucine derivatives of deltorphin I and deltorphin II in rat spinal cord: A search for selectivity of delta receptor subtypesNeuropeptides32(6)511-517(1998)

Dynamin-related GTPase DRP1 partial inhibitor (IC50 = 1.2 μM). Selective for DRP1 over other dynamin-related GTPases, OPA1 and DYN1. Increases mitochondrial DNA levels in mfn1- knockout MEFs deficient in mitochondrial fusion. Mallat et al (2018) Discovery and characterization of selective small molecule inhibitors of the mammalian mitochondrial division dynamin, DRP1. Biochem.Biophys.Res.Commun. 499 556 PMID:29601815

Potent and selective orexin OX2 receptor agonist (EC50 = 28 nM at human OX2 expressed in CHO cells). Displays approximately 100-fold selectivity for OX2 over OX1 (EC50 = 2.75 μM at human OX1 expressed in CHO cells). Depolarizes OX2-expressing histaminergic neurons in mouse brain slices. Increases wake time in wild type mice. Suppresses cataplexy-like symptoms in OX knockout mice. Nagahara et al (2015) Design and synthesis of non-peptide, selective orexin receptor 2 agonists. J.Med.Chem. 58 7931 PMID:26267383 |Irukayama-Tomobe et al (2017) Nonpeptide orexin type-2 receptor agonist ameliorates narcolepsy-cataplexy symptoms in mouse models. Proc.Natl.Acad.Sci.USA. 144 5731 PMID:28507129