refractory

Etripamil (MSP-2017) displays atrioventricular nodal conduction and prolongs atrioventricular nodal refractory periods by inhibiting calcium ion influx through the calcium slow channels in the atrioventricular node cells. Etripamil is an antagonist of short-acting L-type calcium-channel. It has a rapid onset of action designed for intranasal administration. It is also used to treat Paroxysmal Supraventricular Tachycardia.

XRP44X (XRP 44X) is a potent inhibitor of Ras-Net (Elk-3) pathway.

DRF-1042 is an orally active camptothecin analog with antitumor activity and inhibits DNA topoisomerase I. It is used in the study of refractory tumors.

1. Flavokawain B (Flavokavain B) has potent anti-inflammatory activity, can significantly inhibit production of NO and PGE2 in LPS-induced RAW 264.7 cells. 2. Flavokawain B, the hepatotoxic constituent from kava root, induces GSH-sensitive oxidative stress through modulation of IKK/NF-κB and MAPK signaling pathways. 3. Flavokawain B induces apoptosis, has the potential usefulness of FKB for prevention and treatment of hormone-refractory prostate cancer in an adjuvant setting. 4. Flavokawain B acts through ROS generation and GADD153 up-regulation to regulate the expression of Bcl-2 family members, thereby inducing mitochondrial dysfunction and apoptosis in HCT116 cells.

Linvoseltamab, a bispecific antibody, targets both BCMA (TNFRSF17) and CD3 epsilon, demonstrating a favorable safety profile and promising efficacy in relapsed/refractory multiple myeloma (RRMM) [1][2].

Tisagenlecleucel (CTL019), an autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy, selectively targets and eradicates CD19-expressing B cells, and is utilized in the study of refractory aggressive diffuse large B-cell lymphoma [1] [2].

Bersanlimab (BI-505) is a fully human monoclonal antibody targeting Intercellular Adhesion Molecule-1 (ICAM-1).Bersanlimab has anticancer properties and can be used to study relapsed/refractory multiple myeloma.

Glofitamab (RO7082859) is a novel bivalent antibody directed against CD20-binding T cells.Glofitamab promotes T cell proliferation and activation and tumor cell killing by binding to CD20 on malignant cells.Glofitamab can be used for the palliation of relapsed or refractory B-cell lymphomas.

Naptumomab, a tumor-targeting superantigen (TTS), is a fusion protein that activates the immune system to recognize and eradicate tumor cells. It shows promise in researching refractory solid tumors, including renal cell carcinoma [1] [2].

Lucatumumab (HCD122), a fully human anti-CD40 antagonist monoclonal antibody, effectively inhibits CD40/CD40L-mediated signaling and promotes antibody-dependent cell-mediated cytotoxicity (ADCC) for tumor cell clearance. It is applicable in refractory lymphomas, CLL, and multiple myeloma research [1] [2].

Azintuxizumab, an IgG4 bispecific antibody, specifically targets the B-cell maturation antigen (BCMA) and shows promise for the investigation of relapsed/refractory multiple myeloma (RRMM) [1].

Sonoflora 1, also known as SF1, a PDT photosensitivizer. Chemically, SF1 is an analog of chlorophyll in that its macrocycle backbone is porphyrin-based and the center of the porphyrin ring consists of a metal ion. Preclinical studies showed that SF1 had v

EC0489, Small molecule-drug conjugate (SMDC) ,a conjugate of folic acid and desacetyl vinblastine hydrazide, is a high-affinity ligand for the folate receptor (FR). Refractory or metastatic Tumor.

Labetuzumab govitecan is an anti-CEACAM5/SN-38 antibody-drug conjugate for therapy of refractory or relapsing metastatic colorectal cancer.

DRF-1042 HCl is an orally active camptothecin analog with antitumor activity, inhibits DNA topoisomerase I, and is used in the study of refractory solid tumors.

PHI-101 is an orally available and selective checkpoint kinase 2 (Chk2) inhibitor for the study of refractory acute myelogenous leukemia (AML) and ovarian cancer.

Visugromab, a GDF-15 neutralizing IgG4 monoclonal antibody (mAb), demonstrates potent efficacy in treating PD-1/PD-L1 relapsed/refractory metastatic solid tumors [1].

Diphenylcyclopropenone (DPCP) is a topical drug used to treat alopecia areata, alopecia totalis, and refractory warts. Diphencyprone acts as a local stimulator that triggers an immune response against the action of autoreactive cells.

SGI-1776 (Pim-Kinase Inhibitor IX) has been used in trials studying the treatment of Prostate Cancer, Non-Hodgkins Lymphoma, and Relapsed/Refractory Leukemias.

BAY1238097 is a potent and selective bromodomain and extra-terminal motif (BET) inhibitor with anticancer activity that exhibits strong antiproliferative activity in AML (Acute Myeloid Leukemia) and MM (Multiple Myeloma) models.BAY1238097 can be used for the study of advanced refractory malignancies.

Risotilide is a voltage-dependent potassium channel inhibitor. It can prolong cardiac action potentials and refractory periods.

EZM0414 is a potent, selective, orally bioavailable inhibitor of SETD2 with IC50 of 18 nM in SETD2 biochemical assay and IC50 of 34 nM in a cellular assay. EZM0414 can be used for the research of relapsed or refractory multiple myeloma and diffuse large B-cell lymphoma [1].

MFH290 is a novel cysteine (Cys)-directed covalent inhibitor of CDK12/13. MFH290 forms a covalent bond with Cys-1039 of CDK12, exhibits excellent kinome selectivity, inhibits the phosphorylation of serine-2 in the C-terminal domain (CTD) of RNA-polymerase II (Pol II), and reduces the expression of key DNA damage repair genes. Importantly, these effects were demonstrated to be CDK12-dependent as mutation of Cys-1039 rendered the kinase refractory to MFH290 and restored Pol II CTD phosphorylation and DNA damage repair gene expression. Consistent with its effect on DNA damage repair gene expression, MFH290 augments the antiproliferative effect of the PARP inhibitor olaparib.

Dofetilide (UK 68789) is a sulfonamide class III antiarrhythmic agent and potassium channel blocker. Dofetilide selectively blocks cardiac ion channels of the rapid component of the delayed rectifier potassium current Ikr. This antiarrhythmic agent prolongs cardiac action potential duration and effective refractory period due to delayed repolarization without affecting conduction velocity. This results in a normal sinus rhythm. Dofetilide is used in the treatment of atrial fibrillation and flutter.

Lycopodine, a bioactive compound derived from Lycopodium clavatum spores, effectively inhibits the proliferation of HeLa cells through the induction of apoptosis. This process is mediated by caspase-3 activation. In refractory prostate cancer cells, Lycopodine triggers apoptosis by modulating 5-lipoxygenase and depolarizing the mitochondrial membrane potential, without altering p53 activity.

PF05020182 is novel potent and selective Kv7.2/4 potassium channel opener. PF-05020182 (2) significantly inhibits convulsions in the MES assay at doses tested, consistent with in vitro activity measure. The physiochemical properties, in vitro and in vivo activities of PF-05020182 support further development as an adjunctive treatment of refractory epilepsy. Facilitating activation, or delaying inactivation, of the native Kv7 channel reduces neuronal excitability, which may be beneficial in controlling spontaneous electrical activity during epileptic seizures.

Mosunetuzumab (BCT-4465A) is a humanized antibody based on immunoglobulin G1 that targets CD20 (B cells) and CD3 (T cells). Mosunetuzumab redirects T cells to engage and eliminate malignant B cells and can be used to study relapsed or refractory (R/R) B-cell non-Hodgkin lymphoma (B-NHL) and refractory follicular lymphoma.

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

Begelomab (SAND-26), a murine IgG2b monoclonal antibody targeting DPP-4/CD26, has demonstrated utility in investigating severe refractory idiopathic inflammatory myopathy [1] [2].

Neihulizumab (ALTB-168), an immune checkpoint agonistic antibody, targets and binds to human CD162 (PSGL-1), resulting in the downregulation of activated T-cells. It is utilized in research aimed at treating steroid-refractory acute graft-versus-host disease (SR-aGVHD), psoriasis, psoriatic arthritis, and ulcerative colitis [1].

Ozarelix is a fourth generation GnRH antagonist, induces apoptosis in hormone refractory androgen receptor negative prostate cancer cells modulating expression and activity of death receptors. Mechanistically, LHRH antagonists exert rapid inhibition of luteinizing hormone and follicle stimulating hormone with an accompanying rapid decrease in sex hormones and would therefore be expected to be effective in a variety of hormonally dependent disease states including ovarian cancer, prostate cancer, BPH, infertility, uterine myoma and endometriosis. BPH is a non-cancerous enlargement of the prostate that is caused by testosterone. Unlike LHRH agonists, ozarelix has the potential to reduce testosterone just enough to reduce both prostate size and symptoms without the severe side effects associated with a reduction in testosterone.

KCa2 (small conductance Ca2+-activated potassium) channel negative allosteric modulator (IC50 = 1.1 μM). Increases the EC50 of Ca2+ on KCa2.3 channels by ~3-fold. Prolongs atrial effective refractory period (AERP) in rats. Reduces atrial fibrillation (AF) duration and prolongs atrial refractoriness without affecting ventricular refractory period in an animal AF model. Diness et al (2017) Termination of vernakalant-resistant atrial fibrillation by inhibition of small-conductance Ca2+-activated K+ channels in pigs. Circ.Arrhythm.Electrophysiol. 10 e005125 PMID:29018164 |Simó-Vicens et al (2017) A new negative allosteric modulator, AP14145, for the study of small conductance calcium-activated potassium (KCa2) channels. Br.J.Pharmacol. 174 4396 PMID:28925012

Brentuximab is a chimeric antibody targeting CD30 and is a naked antibody to Brentuximab vedotin.Brentuximab has antitumor activity and may be used to study relapsed or refractory Hodgkin's lymphoma.

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.

Invopressin (Compound 42), a vasopressin V1A receptor partial agonist (EC50: 1.0 nM), is utilized in research related to cirrhosis conditions such as bacterial peritonitis, HRS2, and refractory ascites [1].

Mezagitamab (TAK-079), an IgG1λ anti-CD38 monoclonal antibody, functions by depleting tumor cells that express CD38 through both antibody and complement-dependent cytotoxicity. It shows potential for use in the treatment of relapsed/refractory multiple myeloma (RRMM) and idiopathic thrombocytopenic purpura (ITP) [1] [2] [3].

Eliapixant (BAY 1817080) (BAY 1817080) is a potent and selective P2X3 receptor antagonist, with an IC50 of 8 nM. Eliapixant can be used for the research of refractory chronic cough.

Adaprolol maleate is a beta-blocker and opthalmic which may be used in the treatment of Glaucoma or other ailments of the eye. Adaprolol has marked electrophysiologic effects. Its major action was on sinus node; it prolonged the basic sinus cycle length and had significant effect on intrinsic automaticity as reflected by the prolonged corrected sinus node recovery time and sinuatrial conduction time. There was, also, direct effect on atrial function and AV nodal function. Adaprolol prolonged the effective refractory period of the His-Purkinje system and the ventricle. The potency of adaprolol's electrophysiologic effects are higher compared to other widely used beta-blockers. Adaprolol appears to be a potent beta-blocker with particularly strong antiarrhythmic effect and it would be very useful in the treatment of both supraventricular and ventricular tachyarrhythmias and ectopic beats.

CUDC-907 mesylate is a small molecule inhibitor of histone deacetylase and PI3 kinase developed by Curis. It is investigated in clinical trials for the treatment of relapsed or refractory lymphomas, thyroid cancer, multiple myeloma, breast cancer and other malignancies.

Panobinostat lactate is a potent, orally active, non-selective HDAC inhibitor with antitumor effects. Panobinostat lactate can be used to study refractory or relapsed multiple myeloma.

Parsaclisib (INCB050465) is a potent and selective inhibitor of PI3Kδ(IC50 of 1 nM at 1 mM ATP)

D-Allose (β-D-Allopyranose) is a rare naturally occurring monosaccharide known to exert anti-proliferative effects on cancer cells. The effects of D-Allose on the cellular membranes of hormone-refractory prostate cancer cell line (DU145), hormone-sensitive prostate cancer cell line (LNCaP), and normal prostate epithelial cells (PrEC) were studied at the molecular level by phospholipid profiling using a shotgun lipidomic method.

Parsaclisib hydrochloride (INCB050465 HCl) is a selectve PI3Kδ inhibitor with antitumor activity. Parsaclisib demonstrates potent activity with IC50 values ranging from 0.2 to 2 nM.

Altholactone may be a potential antimicrobial agent, particularly in ciprofloxacin-refractory S. aureus and E. faecalis infections. It can inhibit the growth of various types of cancer cells through inducing apoptosis via oxidative stress, including bladd

Valemetostat tosylate is a dual inhibitor of EZH1/2 and used in the research of relapsed/refractory peripheral T-cell lymphoma.

Valnoctamide inhibits benzodiazepine-refractory status epilepticus. Valnoctamide acts directly on GABAA receptors.

AP14145 hydrochloride is a potent negative allosteric modulator of K Ca 2 (SK) channels, specifically targeting K Ca 2.2 (SK2) and K Ca 2.3 (SK3) channels with an IC 50 of 1.1 μM. Inhibition of AP14145 hydrochloride is highly influenced by S508 and A533 amino acids present in the channel. This compound effectively extends the atrial effective refractory period (AERP) in rats and exhibits antiarrhythmic properties in a Vernakalant-resistant porcine model of atrial fibrillation (AF).

CC260, a selective inhibitor for PI5P4Kα and PI5P4Kβ with Kis of 40 nM and 30 nM respectively, exhibits minimal to no inhibition against other protein kinases like Plk1 and RSK2. It is applicable in the research of cell energy metabolism, diabetes, and cancer[1].

Brostallicin is a synthetic, alpha-bromoacrylic, second-generation minor groove binder (MGB), related to distamycin A, with potential antineoplastic activity. Brostallicin binds to DNA minor groove DNA, after having formed a highly reactive glutathione (GSH)-brostallicin complex in the presence of the enzyme glutathione S-transferase (GST), which is overexpressed in cancer cells; DNA replication and cell division are inhibited, resulting in tumor cell death. Compared to typical MGBs, this agent appears to bind covalently to DNA in a different manner and its activity does not depend on a functional DNA mismatch repair (MMR) mechanism. Accordingly, brostallicin may be effective against MMR-defective tumors that are refractory to various anticancer agents.

Ibutilide Fumarate (U70226E) is the fumarate salt form of ibutilide, a class III antiarrhythmic agent. Ibutilide exerts its effect by activating a slow, inward, predominately sodium current rather than by blocking outward potassium currents. This results in prolongation of atrial and ventricular action potential duration and refractory periods. Ibutilide slightly decreases the sinus rate and atrioventricular (AV) conduction and produces a dose-related prolongation of the QT interval.