CSRM617 hydrochloride is a selective small-molecule inhibitor of the transcription factor ONECUT2 ( OC2, a master regulator of androgen receptor) with a K d of 7.43 uM in SPR assays, directly binds to OC2-HOX domain. CSRM617 hydrochloride induces apoptosis through the appearance of cleaved Caspase-3 and PARP. CSRM617 hydrochloride is well tolerated in the mouse model of prostate cancer [1]

Nimodipine (BAY-e 9736), a 1, 4-dihydropyridine calcium channel blocker, acts primarily on vascular smooth muscle cells.

oxepinac is an effective and well-tolerated compound for the treatment of painful osteoarthritis. oxepinac has no teratogenic effect on mouse and rabbit fetuses in animal experiments.

R1498 is an inhibitor of cyclin-dependent kinase 2. It also acts by targeting angiogenesis and mitosis pathways. It is well-tolerated and orally active for hepatocellular carcinoma and gastric cancer treatment.

CP-547632 hydrochloride is a well-tolerated and orally-bioavailable inhibitor of the VEGFR-2 and basic FGF kinases (IC50s: 11 nM and 9 nM) with antitumor efficacy.

OSI-296 is a potent and dual inhibitor of cMET and RON kinases (IC50 value are 42 nM and 200 nM for cMet and sfRon respectively) . OSI-206 shows in vivo efficacy and is well tolerated in tumor xenografts models upon oral dosing. OSI-296 also reduces tumou

Ensartinib (X-396) is a potent and dual ALK/MET inhibitor with IC50s of <0.4 nM and 0.74 nM, respectively. The ability of Ensartinib (X-396) to inhibit the growth of different cancer cell lines harboring ALK fusions or point mutations is tested. Ensartinib is potent in H3122 lung cancer cells harboring EML4-ALK E13;A20 (IC50: 15nM). Ensartinib is also potent in H2228 lung cancer cells harboring EML4-ALK E6a/b; A20 (IC50: 45 nM). Furthermore, X-376 is potent in SUDHL-1 lymphoma cells harboring NPM-ALK (IC50: 9 nM). X-376 also inhibits SY5Y neuroblastoma cells harboring ALK F1174L, MKN-45 gastric carcinoma cells harboring MET dependent, HepG2 cells and PC-9 lung cancer cell lines harboring EGFR exon 19 del with IC50s of 68 nM, 156 nM, 9.644 μM and 2.989 μM, respectively[1]. The effects of Ensartinib (X-396) in vivo against H3122 xenografts are examined. A pharmacokinetic study reveals that Ensartinib shows substantial bioavailability and moderate half-lives in vivo. Nude mice harboring H3122 xenografts are treated with Ensartinib at 25mg/kg bid. Ensartinib significantly delays the growth of tumors compared to vehicle alone. In the xenograft experiments, Ensartinib appears well-tolerated in vivo. Mouse weight is unaffected by Ensartinib treatment. Drug-treated mice appear healthy and do not display any signs of compound related toxicity. To further assess potential side effects of Ensartinib, additional systemic toxicity and toxico-kinetic studies are performed in Sprague Dawley (SD) rats. Following 10 days of repeated oral administration of Ensartinib at 20, 40, 80 mg/kg in SD rats, all animals survive to study termination. The no significant toxicity (NST) levels are determined to be 80mg/kg for Ensartinib. At NST levels, Ensartinib achieves an AUC of 66 μM×hr and a Cmax of 7.19 μM[1]. [1]. Lovly CM, et al. Insights into ALK-driven cancers revealed through development of novel ALK tyrosine kinaseinhibitors. Cancer Res. 2011 Jul 15;71(14):4920-31.

Epalrestat (ONO2235), an aldose reductase inhibitor, is well tolerated in Long-term therapy. It can effectually ameliorate the associated symptoms of diabetic neuropathy and delay the progression of the disease, particularly in patients with limited microangiopathy and good glycemic control.

JNJ-38158471 (CS-2660), a highly selective, orally available, well tolerated VEGFR2 inhibitor with IC50 of 40 nM, inhibits closely related tyrosine kinases such as Ret and Kit with IC50 of 180 nM and 500 nM.

EPI-589, a quinone derivative and oxidoreductase enzyme inhibitor, is considered safe and well tolerated, showing promise for the treatment of amyotrophic lateral sclerosis (ALS).

Antofloxacin is a well-tolerated, orally active, and broad-spectrum 8-amino-fluoroquinolone compound that exhibits potent antibacterial properties. It demonstrates superior activity against gyrA mutation-positive Helicobacter pylori strains, particularly in strains with mutations in the Asn87 position, when compared to levofloxacin. Additionally, Antofloxacin acts as a weak but reversible inhibitor of CYP1A2 and is clinically used to treat infections caused by various bacterial species.

Ipafricept (OMP-54F28; FZD8-Fc), a pioneering recombinant fusion protein, incorporates the extracellular segment of the human frizzled-8 receptor and the Fc fragment of human IgG1, targeting the Wnt ligand. It exhibits activity in inhibiting solid tumors and is well tolerated [1].

Camrelizumab (SHR-1210) is a human IgG4-κ monoclonal antibody with high affinity and directed against PD-1.Camrelizumab binds PD-1 with a binding affinity of up to 3 nM and is inhibitory to PD-1/PD-L1 with an IC50 of 0.70 nM.Camrelizumab exhibits anti-tumor activity and is well tolerated in the study cancers including NSC-LC, ESCC, Hodgkin's lymphoma and advanced HCC.

LY2457546 is a potent and orally bioavailable inhibitor of multiple receptor tyrosine kinases involved in angiogenic and tumorigenic signalling. LY2457546 demonstrates potent activity against targets that include VEGFR2 (KDR), PDGFRβ, FLT-3, Tie-2 and members of the Eph family of receptors. In vivo, LY2457546 inhibited VEGF-driven autophosphorylation of lung KDR in the mouse and rat in a dose and concentration dependent manner. LY2457546 was well tolerated and exhibited efficacy in a 13762 syngeneic rat mammary tumor models. Additionally, LY2457546 caused complete regression of well-established tumors in an acute myelogenous leukemia (AML) FLT3-ITD mutant xenograft tumor model. The unique spectrum of target activity, potent in vivo anti-tumor efficacy in a variety of rodent and human solid tumor models, exquisite potency against a clinically relevant model of AML, and non-clinical safety profile justify the advancement of LY2457546 into clinical testing. (source: Invest New D......

AIC-292 is a potent reverse transcriptase inhibitor with well tolerated in different cell lines. In addition, activity of AIC292 could be demonstrated against a broad panel of wild-type HIV-1 group. AIC292 also retained activity against viruses harboring

Ervogastat (PF-06865571) is a potent and well-tolerated diacylglycerol acyltransferase 2 inhibitor. Ervogastat reduces steatosis and hepatic triglyceride levels in non-alcoholic steatohepatitis (NASH).

BAY-707, a highly potent and selective substrate-competitive inhibitor of MTH1 (NUDT1) with an IC50 of 2.3 nM, is well-tolerated in mice and exhibits a favorable pharmacokinetic (PK) profile compared to other MTH1 compounds. However, it demonstrates a clear lack of anticancer efficacy both in vitro and in vivo[1].

Hetrombopag is a potent agonist of the thrombopoietin receptor. Hetrombopag is well tolerated and has a controlled safety profile. hetrombopag has potential for studies in immune thrombocytopenia.

Balixafortide TFA (POL6326 TFA) is a selective, well-tolerated peptidic CXCR4 antagonist (IC50 < 10 nM). It shows 1000-fold selective for CXCR4 than a large panel of receptors including CXCR7. Balixafortide TFA blocks β-arrestin recruitment and calcium fl

CSRM617 is a selective small molecule inhibitor of the transcription factor ONECUT2 (OC2, the main regulator of androgen receptor). The Kd in SPR analysis is 7.43 uM, which can directly bind to the OC2-HOX domain. CSRM617 induces apoptosis by cleaving the

PF-0463481 is safe and well-tolerated and has the potential for the study of diabetic nephropathy. PF-0463481 is an effective and orally active dual CCR2/CCR5 antagonist. It also has comparable human and rodent CCR2 potency (rat IC50=20.8 nM). PF-0463481

Flobetapir (AV-45) is a well-tolerated imaging compound used in PET scanning. It is synthesized to create Florbetapir (18F), which is a radiopharmaceutical compound containing fluorine-18 radionuclide.

Orvepitant maleate is an effective, selective, and well-tolerated neurokinin-1 receptor (NK-1) antagonist (pKi: 10.2 for human neurokinin-1 receptor). Orvepitant maleate has the potential for depressive disorder and chronic refractory cough (CRC) treatmen

CCG-203971 is an inhibitor of SRE activation in the prostate cancer cell line PC-3 (IC50: 6.4 μM), with 87% inhibition of SRE activation achieved at 100 μM. This compound also inhibits PC-3 cell migration (IC50: 4.2 μM), as determined by a scratch wound assay. CCG-203971(CCG203971) causes no cytotoxicity when evaluated by the WST-1 assay. It is well tolerated in normal mice up to doses of 100 mg/kg given intraperitoneally over five days.

Fluocortin butyl ester is a developed corticosteroid compound with no detectable systemic corticosteroid activity when used topically. fluocortin butyl ester appears to be an effective, well-tolerated topical steroid that can be used in studies of perennial rhinitis.

Suvizumab (KD-247), a neutralizing antibody against HIV-1, effectively neutralizes strains HIV-1 MN, HIV-1 SF2, and HIV-1 89.6, exhibiting IC50 values of 0.1 µg/mL, 1.0 µg/mL, and 0.2 µg/mL, respectively. It demonstrates a significant reduction in viral load, indicating its efficacy in preventing HIV infection. Suvizumab is also well-tolerated, further supporting its potential as a preventative treatment for HIV [1] [2].

Naldemedine (S 297995) is a peripheral selective μ-opioid receptor antagonist being developed by Shionogi for the treatment of opioid-induced adverse reactions, including constipation, nausea, and vomiting. They are usually well tolerated, mainly with mil

G-744 is a selective and orally active inhibitor of Btk (IC50: 2 nM). G-744 is well-tolerated, metabolically stable. It also has an efficacious to treat arthritis.

GDC-0339 is discovered as a potential treatment of multiple myeloma. GDC-0339 is an orally bioavailable and well-tolerated inhibitor of pan-Pim kinase (Kis: 0.03 nM, 0.1 nM and 0.02 nM for Pim1, Pim2 and Pim3, respectively).

GDC-0276, a potent, selective, reversible, and orally active NaV1.7 inhibitor with an IC50 value of 0.4 nM, offers potential for pain treatment while overcoming limitations associated with current pain medications, including addiction and off-target side effects. It is well tolerated and demonstrates a favorable pharmacokinetic profile.

LGB-321 is a potent and selective ATP-competitive small molecule inhibitor of PIM kinases (Pan-PIM kinase inhibitor). LGB321 is unique relative to previously described PIM inhibitors, in that it is active in PIM2 dependent cell lines. , a kinase that has proven difficult to inhibit in the cellular context. Consistent with its activity on all three PIM kinases, LGB321 inhibits proliferation of a number of cell lines derived from diverse hematological malignancies, including MM, AML, CML and B-Cell NHL. In vivo, LGB-321 is orally available, demonstrates efficacy in tumor xenografts and is well-tolerated within the therapeutic exposure range in mice. (source: Clin Cancer Res. 2014 Apr 1;20(7):1834-45 )

Balixafortide (POL6326) is a potent, selective, well-tolerated peptidic CXCR4 antagonist with an IC50 < 10 nM and it is also a potent hematopoietic stem and progenitor cell (HSPC) mobilizing agent. Anti-cancer effects[1][2]. Balixafortide blocks β-arresti

Cilofexor, also known as GS-9674, is a farnesoid X receptor (FXR) agonist. The nonsteroidal FXR agonist cilofexor (GS-9674) improves markers of cholestasis and liver injury in patients with PSC. In clinical study, cilofexor was well tolerated and led to significant improvements in liver biochemistries and markers of cholestasis in patients with PSC.

Verubecestat tosylate, also known as MK-8931 or SCH 900931, is a potent and selective beta-secretase inhibitor, and BACE1 protein inhibitor or Beta-site APP-cleaving enzyme 1 inhibitor. Verubecestat tosylate is a promising novel therapeutic drug candidate in Alzheimer's disease. Verubecestat tosylate reduced Aβ cerebral spinal fluids (CSF) levels up to 92% and was well tolerated by patients.

Propafenone (Propafenonum) is only found in individuals that have used or taken this drug. It is an antiarrhythmia agent that is particularly effective in ventricular arrhythmias. It also has weak beta-blocking activity. The drug is generally well tolerated. The electrophysiological effect of propafenone manifests itself in a reduction of upstroke velocity (Phase 0) of the monophasic action potential. In Purkinje fibers, and to a lesser extent myocardial fibers, propafenone reduces the fast inward current carried by sodium ions, which is responsible for the drugs antiarrhythmic actions. Diastolic excitability threshold is increased and effective refractory period prolonged. Propafenone reduces spontaneous automaticity and depresses triggered activity. At very high concentrations in vitro, propafenone can inhibit the slow inward current carried by calcium but this calcium antagonist effect probably does not contribute to antiarrhythmic efficacy.

Balsalazide sodium hydrate (Balsalazide disodium) is an anti-inflammatory compound used in the treatment of Inflammatory Bowel Disease.Balsalazide sodium hydrate is a new 5-aminosalicylic acid (5-ASA) containing prodrug. High dose Balsalazide sodium hydrate(3.0 g twice daily) was superior in maintaining remission in patients with ulcerative colitis compared with a low dose (1.5 g twice daily) or a standard dose of mesalazine (0.5 g three times daily). All three treatments were safe and well tolerated [1]. Balsalazide sodium hydrate is approved for the treatment of mild-to-moderate active UC. It is efficacious for the induction of remission in mild to moderate UC and has a favorable safety profile, with the added advantages of greater efficacy of remission induction and rapidity of onset [2].

NP213 TFA, a novel, first-in-class synthetic antimicrobial peptide (AMP) with rapid anti-fungal action, targets the fungal cytoplasmic membrane, resulting in perturbation and disruption. It has been demonstrated to be effective and well-tolerated in treating nail fungal infections [1] [2].

PKI-179 is a potent, orally active compound that functions as a dual PI3K/mTOR inhibitor. It demonstrates IC50 values of 8 nM for PI3K-α, 24 nM for PI3K-β, 74 nM for PI3K-γ, 77 nM for PI3K-δ, and 0.42 nM for mTOR. Additionally, it is effective against E545K and H1047R mutations, with IC50s of 14 nM and 11 nM, respectively. In vivo studies have shown that PKI-179 possesses anti-tumor capabilities[1][2].

Pipebuzone is an anti-inflammatory, antipyretic and analgesic drug used in the treatment of various rheumatic diseases. It is well tolerated clinically and pathologically and has a reliable anti-inflammatory effect.

(+/-)- Adomeglivant, also known as LY2409021, is a potent and selective glucagon receptor antagonist. LY2409021 lowers blood glucose in healthy people and in those with type 2 diabetes. Blockade of glucagon signalling in patients with type 2 diabetes is well tolerated and results in substantial reduction of fasting and postprandial glucose with minimal hypoglycaemia, but with reversible increases in aminotransferases. Inhibition of glucagon signalling by LY2409021 is a promising potential treatment for patients with type 2 diabetes and should be evaluated in longer clinical trials to better evaluate benefits and risks.

Amidantel free base is a new aminophenylamidine with an interesting anthelminthic spectrum. In rodents the compound is active against nematodes, filariae and cestodes. Of special interest is the high efficacy in dogs against hookworms and large roundworms

Dextrorotation nimorazole phosphate ester is an anti-anaerobic and anti-parasitic agent. D-morpholine ornidazole organic phosphate is a newly developed, highly efficient, well-tolerated fourth-generation nitroimidazole derivative. Objective: Antibacterial

Zotatifin is a potent and well-tolerated eIF4A inhibitor. Zotatifin promotes eIF4A binding to specific mRNA sequences with recognition motifs in the 5’-UTRs (IC50=2 nM). Zotatifin effectively reduces viral infectivity by inhibiting SARS-CoV-2 NP protein b

SMU-B is a well-tolerated c-Met/ALK dual inhibitor.

NP213 is a rapidly acting synthetic antimicrobial peptide (AMP). NP213 is effective and well-tolerated in resolving nail fungal infections. NP213 has anti-fungal activities. NP213 targets the fungal cytoplasmic membrane and plays its role via membrane perturbation and disruption.

Sodium thiosulfate (Pentahydrate) is an antioxidant and antifungal. Sodium thiosulfate protects against cisplatin-induced hearing loss in children and is not associated with serious adverse events attributed to its use[3]. The addition of sodium thiosulfate, administered 6 hours after cisplatin chemotherapy, resulted in a lower incidence of cisplatin-induced hearing loss among children with standard-risk hepatoblastoma, without jeopardizing overall or event-free survival[4]. Calciphylaxis is a potentially fatal disorder of abnormal calcium deposition. Treatment is multifaceted, and improved outcomes have been demonstrated with intravenous sodium thiosulfate; however, the use of this medication can be limited by its adverse effects[5]. TST (topical sodium thiosulfate) appears to be a relatively well-tolerated adjuvant treatment for CC(calcinosis cutis)[6]. The combined treatment of sodium thiosulfate, pamidronate and calcitomimetics has been effective and safe for the treatment of calciphylaxis, inducing complete remission[7].

Clomifene hydrochloride can induce ovulation and can be used in infertility. hydrochloride is a simple, relatively safe, easy to administer and well tolerated, orally active compound.

BMS-962212, a direct, reversible, and selective factor XIa (FXIa) inhibitor, demonstrates fast pharmacodynamic (PD) response onset and rapid elimination with a well-tolerated profile. It dependently increases activated partial thromboplastin time and decreases FXI clotting activity exposure [1].

Mosnodenvir (JNJ-1802), a pan-serotype dengue antiviral agent, exhibits picomolar to low nanomolar in vitro activity with a high barrier to resistance and is safe and well-tolerated in murine models [1] [2]. It functions by blocking the NS3-NS4B interaction within the viral replication complex.

Levodropropizine ((S)-(-)-Dropropizine) is a histamine receptor inhibitor. It is used as an effective and very well tolerated peripheral antitussive drug.