refractory

Etripamil (MSP-2017) 是一种短效L 型钙通道拮抗剂，可用于治疗阵发性室上性心动过速的研究。它通过抑制房室结细胞中钙慢通道的钙离子流入，显示房室结传导并延长房室结不应期

NSC-639829 是一种 Benzoylphenylurea (BPU) 类似物，具有抗肿瘤活性的，可用于研究难治性转移性肿瘤。

Dofetilide (UK 68789) 是一种具有口服活性、有效的且特异性的IKr 阻滞剂，作为 III 类抗心律失常药物。Dofetilide 可用于心血管疾病研究。

Propafenone (Propafenonum) 是钠通道阻滞剂，它对 β 受体具有高亲和力 (IC50=32 nM)。它能够阻断瞬时外向钾电流 (Ito) (IC50: 4.9 nM) 和持续延迟整流器K+电流 (Isus) (IC50: 8.6 nM) ，具有抗心律失常的作用。它能够诱导线粒体功能障碍及诱导细胞凋亡，从而抑制食管癌增殖。

DRF-1042 HCl 是一种具有口服活性的喜树碱类似物，具有抗肿瘤活性，抑制 DNA 拓扑异构酶 I，可用于研究难治性实体瘤。

XRP44X (XRP 44X) 是Ras 诱导的转录激活的抑制剂，IC50为 10 nM，通过 FGF-2 抑制 Ras-Erk-1 2 通路激活。它抑制Elk3。它还对微管有影响。

DRF-1042 是一种具有口服活性的喜树碱类似物，具有抗肿瘤活性，抑制 DNA 拓扑异构酶 I，可用于研究难治性肿瘤。

Flavokawain B (Flavokavain B) 是从卡瓦醉椒的根提取物中，分离出的查尔酮。它是一种凋亡诱导剂，可抑制各种癌细胞株生长。它以极低的无毒浓度抑制人脑内皮细胞的迁移和血管形成，具有抗血管生成活性。

EZM0414 是一种有效、选择性、口服生物利用度高的SETD2抑制剂，在 SETD2 生化分析中，IC50值为18 nM；在细胞分析中，IC50值为34 nM。EZM0414可用于复发或难治性多发性骨髓瘤和弥漫性大 B 细胞淋巴瘤的研究。

Eliapixant (BAY 1817080) 是一种选择性的P2X3受体拮抗剂，IC50值为 8 nM，可用于难治性慢性咳嗽的研究。

Diphenylcyclopropenone (DPCP) 是局部免疫调节剂，可用于研究斑秃。

Linvoseltamab为双特异性抗体，针对BCMA(TNFRSF17)与CD3epsilon。该化合物于复发 难治性多发性骨髓瘤(RRMM)模型中展示了良好的安全性和效力。

Tisagenlecleucel (CTL019) 是一种自体抗CD19嵌合抗原受体 (CAR) T 细胞治疗，专门针对并消除表达CD19的 B 细胞。该疗法主要用于研究治疗难治性侵袭性弥漫性大 B 细胞淋巴瘤。

LY2623091 是一种盐皮质激素受体拮抗剂，适用于抑制难治性高血压。LY2623091 显示清除能力依赖于CYP3A4，并与CYP3A4抑制剂表现出协同作用。

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

Moricizine Hydrochloride (EN 313) 是一种口服具有活力的 I 类抗心律失常剂。Moricizine Hydrochloride 能够减少 0 相去极化的速率；提高 2 相和 3 相复极率，降低动作电位持续时间，减少有效不应期。

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.

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 (BTCT-4465A) 是一种基于免疫球蛋白 G1 且靶向 CD20 (B 细胞) 和 CD3 (T 细胞) 的人源化抗体。Mosunetuzumab 重定向 T 细胞以接合和消除恶性 B 细胞，可用于研究复发或难治性 (R R) B 细胞非霍奇金淋巴瘤 (B-NHL)和难治性滤泡性淋巴瘤。

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.

SGI-1776 (Pim-Kinase Inhibitor IX) 是一种Pim 抑制剂，抑制 Pim-1、Pim-2 和 Pim-3 的活性，IC50值分别为 7 nM、363 nM 和 69 nM。

BAY1238097 是一种具有有效性和选择性的溴结构域和末端外基序(BET)抑制剂，具有抗癌活性，在AML (急性髓性白血病) 和MM (多发性骨髓瘤) 模型中表现出较强的抗增殖活性 。BAY1238097 可用于研究晚期难治性恶性肿瘤。

Neihulizumab (ALTB-168) 是一种免疫检查点激动性抗体，可与人 CD162 (PSGL-1)结合，导致活化的 T 细胞下调。Neihulizumab 可用于类固醇难治性急性移植物抗宿主病 (SR-aGVHD)、银屑病、银屑病关节炎和溃疡性结肠炎的研究。

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.

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

Bersanlimab (BI-505) 是一种全人源靶向细胞间粘附分子-1 (ICAM-1）的单克隆抗体。Bersanlimab 具有抗癌作用，可用于研究复发 难治性多发性骨髓瘤。

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

Begelomab (SAND-26) 是一种针对 DPP-4/CD26的鼠IgG2b 单克隆抗体。 Begelomab 可用于严重难治性特发性炎症性肌病的研究。

Glofitamab (RO7082859) 是一种新型针对 CD20 结合 T 细胞的二价抗体。Glofitamab 通过与恶性细胞上的 CD20 结合促使 T 细胞增殖活化和肿瘤细胞杀伤。Glofitamab 可用于缓解复发或难治性 B 细胞淋巴瘤。

Brentuximab 是靶向 CD30 的嵌合抗体，是 Brentuximab vedotin 的裸抗。Brentuximab 具有抗肿瘤活性，可用于研究复发或难治性霍奇金淋巴瘤。

Naptumomab是一种针对肿瘤细胞的超级抗原(TTS)融合蛋白。它能激活免疫系统，使之识别并消灭肿瘤细胞。该化合物主要应用于肾细胞癌等难治性实体肿瘤的研究领域。

Invopressin (Compound 42)，一种vasopressin V1A 受体部分激动剂（EC50: 1.0 nM），主要应用于肝硬化相关症状如细菌性腹膜炎、HRS2 及难治性腹水的研究。

Azintuxizumab是针对B细胞成熟抗原(BCMA)的IgG4型双特异性单克隆抗体，显示出在治疗复发/难治性多发性骨髓瘤(RRMM)中的应用潜力。

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.

Molibresib besylate (GSK 525762C) 是一种具有选择性和高效性的溴结构域和末端外 （BET） 蛋白家族抑制剂，具有潜在的抗癌活性，可用于研究难治性血液系统恶性肿瘤疾病。Molibresib besylate 产生活性氧 （ROS），增强 ATM 激活。

Panobinostat lactate 是一种有效的、口服具有活力的、非选择性 HDAC 抑制剂，具有抗肿瘤作用。Panobinostat lactate 诱导细胞凋亡 (apoptosis) 和自噬 (autophagy)。Panobinostat lactate 能够有效干扰 HIV 潜伏期。Panobinostat lactate 能够用于研究难治性或复发性多发性骨髓瘤。

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.

Lucatumumab (HCD122) 是一种全人抗 CD40拮抗剂单克隆抗体，可阻断 CD40/ CD40L 介导的信号通路。Lucatumumab 可有效介导抗体依赖性细胞介导的细胞毒性 (ADCC) 和肿瘤细胞清除，可用于顽固性淋巴瘤、慢性淋巴细胞白血病 (CLL) 和多发性骨髓瘤研究。

Mezagitamab (TAK-079) 是一种 IgG1λ 类型的抗CD38单克隆抗体。其通过促进抗体和补体依赖性的细胞毒性，来耗尽表达CD38的肿瘤细胞，显示出在复发/难治性多发性骨髓瘤 (RRMM) 及原发性血小板减少性紫癜 (ITP) 等疾病中的治疗潜力。

Parsaclisib hydrochloride (INCB050465 HCl) 是一种选择性的、有效的，具有口服活性的 PI3Kδ抑制剂，IC50=1 nM。它相对于其他 PI3K I 类同工型的选择性约为 20000 倍。它可用于复发或难治性 B 细胞恶性肿瘤的研究。

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

PHI-101 是一种可口服且具有选择性的检查点激酶 2 （Chk2） 抑制剂，可用于研究难治性急性髓系白血病（AML）和卵巢癌。

Parsaclisib (INCB050465) 是有效的、选择性的、具有口服活性的PI3Kδ抑制剂，其 IC50=1 nM。它相对于其他 PI3K I 类同工型的选择性约为 20000 倍。它可用于复发或难治性 B 细胞恶性肿瘤的研究。

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.

BA6b9 是SK4 通道变构抑制剂，针对 CaM-PIP2 结合结构域。该化合物通过与 S4-S5 连接处的 Arg191 和 His192 两个关键残基互作，达到抑制 SK4 通道的效果，其 IC50 值为 8.6 μM (WT SK4)。此外，BA6b9 能显著延长大鼠分离心脏的心房和房室有效不应期(ERP)，减少心房颤动(AF)的发生，显示出其在心律失常研究中的应用潜力。

D-Allose (β-D-Allopyranose) 是内源性代谢产物的一种。

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

CC260 is a selective PI5P4Kα and PI5P4Kβ inhibitor with Kis of 40 nM and 30 nM, respectively. CC260 does not inhibit or weakly inhibits other protein kinases, such as Plk1 and RSK2. CC260 can be used for cell energy metabolism, diabetes and cancer research[1]. In cultured C2C12 myotubes, CC260 (20 μM) enhances Insulin-induced Akt phosphorylation at both Thr-308 and Ser-473 but suppresses S6K phosphorylation (Thr-389) by mTORC1[1]. CC260 (2.5 μM, 5 μM, 10 μM, 20 μM) significantly increases phosphorylation of acetyl-CoA carboxylase (ACC) in a dose-dependent manner[1]. CC260 treatment reduces the ability of BT474 cells to survive serum starvation, which could be rescued by expressing the PI5P4Kβ refractory mutant[1]. In BT474 cells, CC260 treatment causes an increase in glycolytic ATP production[1]. [1]. Song Chen, et al. Pharmacological inhibition of PI5P4Kα β disrupts cell energy metabolism and selectively kills p53- tumor cells. Proc Natl Acad Sci U S A. 2021 May 25;118(21):e2002486118.