high oral bioavailability

ELN-441958是一种B1受体拮抗剂，能够抑制B1激动剂配体[3H] DAKD 与IMR-90细胞结合(Ki:0.26 nM)，相较于B2受体，它对B1受体的抑制作用具有更高的选择性，且比抑制μ阿片受体选择性高500多倍，比抑制δ阿片受体选择性高2000多倍。

BMS-929075是一种具有口服活性 HCV NS5B 复制酶 (HCV NS5B replicase) 手掌位点变构抑制剂，具有有效性、 较高的口服生物利用度和药代动力学参数 。BMS-929075 显示出细胞毒性。

Alpelisib hydrochloride (BYL-719 hydrochloride) shows antineoplastic activity[1][2]. Alpelisib hydrochloride (BYL-719 hydrochloride) is a potent, orally active, and selective PI3Kα inhibitor with IC50s of 5 nM, 250 nM, 290 nM and 1200 nM for p110α, p110γ,

MerTK Axl-IN-1 (Compound A-910) 作为一种高效且具选择性的MerTK Axl双重抑制剂，其在Ba F3细胞中的IC50值为4.2和8.8 nM，在HTRF细胞中的IC50为0.2和0.9 nM。该化合物能有效抑制体内pMerTK，同时具备优良的半衰期与高口服生物利用度。

EGFR-IN-132（Compound 23）为一种有效的EGFR抑制剂，能够针对不同的突变体如EGFR野生型、L858R T790M、d19 T790M、L858R T790M C797S 及 d19 T790M C797S 实现抑制，其IC50值分别为1.6、0.025、0.019、0.022 和 0.029 nM。该化合物展示出优异的药代动力学属性，并且在口服给药时显示高暴露度。

EGFR-IN-133（Compound 24）作为一种有效的EGFR抑制剂，针对EGFR野生型及其L858R T790M、d19 T790M、L858R T790M C797S和d19 T790M C797S的突变体显示出低纳摩尔级的抑制活性，其IC50分别为0.1、0.044、0.036、0.04和0.054 nM。此外，EGFR-IN-133展现出优异的药代动力学属性，并具有高口服暴露度。

Emavusertib Maleate（亦称CA-4948）是一种高效的IRAK4 FLT3抑制剂，具有抗肿瘤活性。在ABC DLBCL和AML细胞系中，CA-4948展现了良好的细胞活性。它在329种激酶的选择性测试中表现出中到高的选择性，并且在ADME和PK配置文件中显示出良好的口服生物利用度，包括在小鼠、大鼠和狗中的良好吸收。在相关的肿瘤模型中，CA-4948展示了超过90%的肿瘤生长抑制，并且与体内PD调节显示出极好的相关性。

Emavusertib Tosylate（亦称CA-4948）是一种有效的IRAK4 FLT3抑制剂，具有抗肿瘤活性。在ABC DLBCL和AML细胞系中，CA-4948展现了良好的细胞活性。该化合物在329种激酶的评估中表现出中到高的选择性，并且在ADME和PK配置文件中展示出良好的口服生物利用度和优良的药代动力学特性。在小鼠、大鼠和狗的模型中，CA-4948展示了良好的口服生物利用性，并在相关肿瘤模型中显示出超过90%的肿瘤生长抑制效果，与体内PD调节具有极好的相关性。

Emavusertib Mesylate（又名CA-4948）是一种效力显著的IRAK4 FLT3抑制剂，具有抗肿瘤活性。在ABC DLBCL和AML细胞系中，CA-4948展示了良好的细胞活性。此外，CA-4948在329种激酶的筛选实验中显示出中到高的选择性，并且在药代动力学和药效学（ADME和PK）档案中表现出色，包括在小鼠、大鼠和狗中具有良好的口服生物利用度。在相关的肿瘤模型中，CA-4948显示出超过90%的肿瘤生长抑制，并与体内PD调制有优秀的相关性。

Emavusertib Phosphate（又名CA-4948）是一种强效的IRAK4 FLT3抑制剂，具有抗肿瘤活性。在ABC DLBCL和AML细胞系中，CA-4948显示出良好的细胞活性。此外，CA-4948在一个由329种激酶组成的面板中表现出中到高的选择性，并展示了理想的ADME和PK特性，包括在小鼠、大鼠和狗中良好的口服生物利用度。在相关肿瘤模型中，CA-4948展示了超过90%的肿瘤生长抑制效果，并与体内PD调节呈现出优秀的相关性。

PDE5-IN-13 (Compound 14b) 抑制磷酸二酯酶 5 (PDE5A) 的IC50为3 nM，用于肺动脉高压研究。与PDE1、PDE2、PDE3、PDE4、PDE7、PDE8、PDE9、PDE10和PDE11相比，PDE5-IN-13 对靶点显示出高选择性，并且具有口服活性。

CK1δ-IN-9 (Compound 8) 是一种酪蛋白激酶1的抑制剂，可有效抑制CK1δ，其IC50值为1.4 nM。该化合物同时抑制p38α和p38β，IC50分别为0.25 μM和0.78 μM。CK1δ-IN-9 具备出色的药代动力学特性，且口服生物利用度高达70%，清除率适中。

FR-181877, a nonprostanoid PGI2 agonist, inhibits ADP-induced aggregation of human platelets with an IC50 value of 0.081 microM and has high oral bioavailability (56%) with a long half-life (4.3 h) in rats.

PI3Kα-IN-4 is a potent, selective and orally active inhibitor of PI3Kα, with an IC50 of 1.8 nM. PI3Kα-IN-4 has antitumor activity[1]. PI3Kα-IN-4 (compound 10) inhibits PI3Kα, β, δ, and γ, with IC50s of 1.8, 271.0, 13.9, and 13.8 nM, respectively in kinase assays[1].PI3Kα-IN-4 inhibits PI3Kα, β, δ, and γ, with IC50s of 12.1,1393, 183, and >10000 nM, respectively in cell based assays[1]. PI3Kα-IN-4 (compound 10) (30 mg kg; p.o. once daily for 21 d) achieves the best efficacy, which could inhibit tumor growth by 73.0% in mice[1].PI3Kα-IN-4 (15-40 mg kg; p.o. once daily for 30 d) dose dependently suppresses tumor growth by 62.5% (15 mg kg), 86.0% (30 mg kg) and 90.7% (40 mg kg), respectively in mice[1].PI3Kα-IN-4 (15-40 mg kg; p.o. once daily; 1-4 h) inhibits the phosphorylation of Akt in a dose- and time-dependent manner in vivo[1].PI3Kα-IN-4 shows high Cmax (mouse 22167, rat 2327 nM) and good bioavailability (mouse 59.4%, rat 46.9%) following oral administration (mouse 10, rat 3 mg kg)[1].PI3Kα-IN-4 shows t1 2 (mouse 0.99, rat 1.22 h) and low plasma clearance (mouse 4.16, rat 5.28 mL min kg) following intravenous injection (mouse 1, rat 1 mg kg)[1]. [1]. Dong J, et, al. Discovery of 3-Quinazolin-4(3 H)-on-3-yl-2, N-dimethylpropanamides as Orally Active and Selective PI3Kα Inhibitors. ACS Med Chem Lett. 2020 Jun 10; 11(7): 1463-1469.

PKI-179 is a potent and orally active dual PI3K mTOR inhibitor, with IC50s of 8 nM, 24 nM, 74 nM, 77 nM, and 0.42 nM for PI3K-α, PI3K-β, PI3K-γ, PI3K-δ and mTOR, respectively. PKI-179 also exhibits activity over E545K and H1047R, with IC50s of 14 nM and 11 nM, respectively. PKI-179 shows anti-tumor activity in vivo[1][2]. PKI-179 inhibits the cell proliferation, with IC50s of 22 nM and 29 nM for MDA361 and PC3 cells, respectively[1].PKI-179 shows inhibitory activity against a panel of 361 other kinases, hERG and cytochrome P450 (CYP) isoforms at concentrations up to >30 μM, but does have activity for CYP2C8 (IC50=3 μM)[1]. PKI-179 (5-50 mg kg; p.o. once daily for 40 days) inhibits the tumor growth and is well tolerated in nude mice bearing MDA-361 human breast cancer tumors[1].PKI-179 (50 mg kg; p.o.) results in good inhibition of PI3K signaling in nude mice bearing MDA361 tumor xenografts[1].PKI-179 exhibits good oral bioavailability (98% in nude mouse, 46% in rat, 38% in monkey, and 61% in dog) and a high half-life (>60 min) [1]. [1]. Venkatesan AM, et, al. PKI-179: an orally efficacious dual phosphatidylinositol-3-kinase (PI3K) mammalian target of rapamycin (mTOR) inhibitor. Bioorg Med Chem Lett. 2010 Oct 1;20(19):5869-73.[2]. Rehan M. A structural insight into the inhibitory mechanism of an orally active PI3K mTOR dual inhibitor, PKI-179 using computational approaches. J Mol Graph Model. 2015 Nov;62:226-234.

mGluR2 antagonist 1 is a potent and selective class of negative allosteric modulator targeting the metabotropic glutamate receptor 2 (mGluR2) with high oral bioavailability. It displays a remarkable affinity for mGluR2, with an IC50 value of 9 nM. Furthermore, it exhibits excellent permeability across the blood-brain barrier, making it a promising candidate for central nervous system-related studies or therapies.

FXIa-IN-6 是一种有效的 FXIa 抑制剂，对大多数相关丝氨酸蛋白酶具有选择性（Ki= 0.3 nM）。FXIa-IN-6 还在多个临床前物种中展示了出色的药代动力学 (PK) 特性（高口服生物利用度和低清除率）。

KRH-3955 hydrochloride is a CXCR4 antagonist with oral bioavailability. It effectively inhibits the binding of SDF-1α to CXCR4, exhibiting an IC 50 of 0.61 nM. Additionally, KRH-3955 hydrochloride displays high potency and selectivity as an inhibitor of X4 HIV-1, with an EC 50 ranging from 0.3 to 1.0 nM.

AAK1-IN-5 is a potent and specific inhibitor of adaptor protein-2-associated kinase 1 (AAK1), characterized by its ability to penetrate the central nervous system and its oral bioavailability. It displays high selectivity, with an AAK1 inhibitory potency (IC 50) of 1.2 nM, a binding affinity (K i) of 0.05 nM, and an inhibitory potency against cellular AAK1 activity (cell IC 50) of 0.5 nM. AAK1-IN-5 holds promise for investigating neuropathic pain in scientific research [1].

MPT0G211 mesylate is a powerful and selective HDAC6 inhibitor (IC50 = 0.291 nM), with high oral bioavailability. It exhibits remarkable selectivity for HDAC6 over other HDAC isoforms (>1000-fold selectivity). Additionally, MPT0G211 mesylate can effectively cross the blood-brain barrier. In preclinical studies using an Alzheimer's disease model, MPT0G211 mesylate has shown promising results in reducing tau phosphorylation and cognitive deficits. Furthermore, this compound exhibits anti-metastatic and neuroprotective effects, making it a potential candidate for anticancer interventions. [1] [2] [3].

HIV-1 inhibitor-15 (compound 9d) is a potent and broad-spectrum inhibitor targeting HIV-1. It exhibits inhibitory activity against HIV-1 WT, L100I, K103N, Y181C, and E138K with respective EC50 values of 1.7 nM, 4 nM, 2 nM, 6 nM, and 9 nM. In addition to its high efficacy, HIV-1 inhibitor-15 possesses favorable solubility, safety profiles, and oral bioavailability [1].

JAK3-IN-9 is a potent and orally active inhibitor of the Janus kinase 3 (JAK3) enzyme, displaying an impressive IC50 value of 1.7 nM. It exhibits high selectivity towards the JAK3 signaling pathway, making it a valuable tool for studying autoimmune diseases. Additionally, JAK3-IN-9 possesses desirable characteristics such as low toxicity and excellent oral bioavailability. It also demonstrates promising anti-arthritis activity, thus enhancing its potential as a therapeutic agent [1].

SNJ-1945 is a calpain inhibitor with more favorable retinal penetration, high oral bioavailability, and long half-life. SNJ1945 rescued defective function in lissencephaly. SNJ-1945 protects SH-SY5Y cells against MPP(+) and rotenone. SNJ-1945 reduces murine retinal cell death in vitro and in vivo. SNJ-1945 has good aqueous solubility, can prevents the heart from KCl arrest-reperfusion injury associated with the impairment of total Ca(2+) handling by inhibiting the proteolysis of alpha-fodrin as a cardioplegia.

Etozolin HCl is a safe and effective diuretic agent in the treatment of acute cardiac failure. In isolated rings of guinea-pig aorta not responding to acetylcholine, the diuretic dexetozoline did not influence basal vascular tone but inhibited noradrenaline- and histamine-induced contractions. Dexetozoline has a very high bioavailability after oral administration and is fairly lipohilic. The half-life of etozolin is 2.5 h. Dexetozoline accumulates in cirrhosis.