akr

AKR1C1-IN-1 is a human 20α-hydroxysteroid dehydrogenase (AKR1C1) inhibitor (Ki: 4 nM for AKR1C1).

AKR1C3-IN-4, a potent and selective inhibitor of aldo-keto reductase 1C3 (AKR1C3) with an IC50 of 0.56 μM, shows potential for castrate-resistant prostate cancer (CRPC) research.

AKR1B10-IN-1, a powerful AKR1B10 (Aldo-Keto Reductase 1B10) inhibitor, demonstrates an IC50 value of 3.5 nM. This compound effectively curtails the proliferation, metastasis, and Cisplatin (CDDP) resistance of lung cancer cells.

Rutin (Quercetin 3-O-rutinoside), a flavonoid, has a variety of biological activities including antiallergic, anti-inflammatory, antiproliferative, and anticarcinogenic properties.

Avatrombopag (YM477) is a new oral thrombopoietin (TPO) receptor agonist, activating TPO receptor and increasing megakaryocytic proliferation/differentiation and platelet production.

Avatrombopag hydrochloride (AKR-501) is an orally active, nonpeptide agonist of the thrombopoietin (TPO) receptor with an EC50 of 3.3 nM. It effectively mimics TPO by stimulating platelet production through activation of the intracellular signaling system, facilitating platelet and megakaryocyte generation from hemopoietic precursor cells. Additionally, Avatrombopag hydrochloride serves as a substrate for cytochrome P450 [CYP] 2C9 and CYP3A.

Avatrombopag, also known as AKR-501, YM477, AS 1670542 or E5501, is a novel orally-active thrombopoietin (TPO) receptor agonist. AKR-501 specifically targeted the TPO receptor and stimulated megakaryocytopoiesis throughout the development and maturation of megakaryocytes just as rhTPO did. AKR-501 may be useful in the treatment of patients with thrombocytopenia. Avatrombopag was first approved in 2018.

AKR1C3-IN-9, a selective Aldo-keto Reductase 1C3 (AKR1C3) inhibitor (IC50 = 8.92 nM), can significantly reverse Doxorubicin (DOX) resistance in a resistant breast cancer cell line.

AKR1C3-IN-1 is a potent and selective inhibitor of AKR1C3(IC50 of 13 nM).

AKR1Cs-IN-1 (Compound 29) is an effective and broad-spectrum inhibitor of the Aldo-Keto Reductase 1C family (AKR1C1-1C4). It achieves subtype inhibition by simultaneously binding to the SP2 and SP3 pockets, thereby blocking metabolic pathways related to drug resistance. In enzyme assays, AKR1Cs-IN-1 exhibits significant inhibitory activity with IC50 values of 0.09, 0.28, 0.05, and 0.51 µM for AKR1C1, AKR1C2, AKR1C3, and AKR1C4, respectively. The compound shows excellent resensitizing effects in doxorubicin (DOX)-resistant breast cancer cell line MCF-7/ADR, effectively enhancing the cytotoxicity of DOX. AKR1Cs-IN-1 holds promise for research on breast cancer resistance.

AKR1C3-IN-15 (compound 30) is an effective and selective AKR1C3 inhibitor with an IC50 value of 5 nM. It enhances Sorafenib-induced ROS production, promotes apoptosis, and restores sensitivity to Sorafenib in hepatocellular carcinoma (HCC) models, as demonstrated in both in vitro and in vivo studies.

AKR1C3-IN-11 (Compound 6e) is an inhibitor of aldehyde ketone reductase 1C3 (AKR1C3) with an IC50 of 2.0 μM. When combined with abiraterone, AKR1C3-IN-11 can suppress cell proliferation and is applicable in prostate cancer research.

PROTACAKR1C3 degrader-1 (compound 5) is an efficient AKR1C3 PROTAC degrader. It effectively reduces the protein expression of AKR1C3, AKR1C1/2, and ARv7. PROTACAKR1C3 degrader-1 shows potential for research in prostate cancer.

AKR1C3-IN-13 (Compound 4) is an inhibitor of AKR1C3. It can degrade AKR1C3 within prostate cancer cells.

AKR1C2/3-IN-1 (compound 3a) is a potent inhibitor of AKR1C2 and AKR1C3, with IC50 values of 90 nM and 50 nM, respectively. It serves as a radiosensitizer and an enhancer of the cytotoxicity of chemotherapy.

AKR1B1/STAT3/SLC7A11-regulator-1 (5a) is a modulator of the AKR1B1/STAT3/SLC7A11 pathway, capable of reversing DOX resistance in MCF-7/ADR cells by enhancing ferroptosis (apoptosis) activity. It is utilized in breast cancer research.

AKR1C3-IN-6 (Compound 1) is a potent and specific AKR1C3 inhibitor, exhibiting IC50 values of 0.31 μM against AKR1C3 and 73.23 μM against AKR1C2. It demonstrates significant antitumor activity [1].

AKR1C3-IN-7 (Compound 13) is a potent and selective AKR1C3 inhibitor with an IC50 of 0.19 μM, exhibiting antitumor activity.

AKR1C3-IN-8 (Compound 5) is a potent and selective AKR1C3 inhibitor (IC50 = 0.069 μM) with demonstrated antitumor activity.

AKR1C3-IN-5 (Compound 6e) is a potent inhibitor of AKR1C3, derived from drupanin, with significant activity against MCF-7 cells (IC50: 9.6 ± 3 μM; SI: 5.5). AKR1C3 enzymes are overexpressed in hormone-dependent prostate and breast tumors.

PTP1B/AKR1B1-IN-1 is a dual inhibitor targeting protein tyrosine phosphatase 1B (PTP1B) and aldose reductase (AKR1B1), with IC50s of 0.06 μM for PTP1B and 4.3 μM for AKR1B1. It also inhibits T-cell protein tyrosine phosphatase (TC-PTP) with an IC50 of 9 μM. This compound acts as an insulin-mimetic in murine myoblasts, reduces AKR1B1-mediated sorbitol accumulation, and aids in managing blood glucose levels and inhibiting type 2 diabetes mellitus (T2DM) development [1].

PTP1B/AKR1B1-IN-2 (Compound 7f) is a potent inhibitor targeting both PTP1B and AKR1B1 with IC50 values of 3.2 and 2.1 μM, respectively, and K i values of 4.0 and 0.9 μM. This compound acts as an insulin mimetic and enhances glucose uptake in murine C2C12 myoblasts, making it useful for Type 2 diabetes mellitus (T2DM) research [1].

AKR1C3-IN-10 (compound 5r), a selective inhibitor of AKR1C3 with an IC50 of 51 nM, demonstrates efficacy in a prostate cancer xenograft model [1].

AKR1C3-IN-12 (compound 2j), an inhibitor of aldo-keto reductase 1C3 (AKR1C3), exhibits potent activity with an IC50 of 27 nM. It has been shown to enhance the effectiveness of Gemcitabine and Cisplatin in treating bladder cancer [1].