hematopoietic prostaglandin synthase

Pizuglanstat 是一种前列腺素 D 合酶抑制剂，对人造血前列腺素 D 合酶的IC50为 76 nM，可用于肌再生性疾病研究。

PROTAC(H-PGDS)-7 是一种有选择性的、有效的小分子造血前列腺素 D 合酶 （H-PGDS）PROTAC 降解剂，在 KU812细胞中展现出降解活性，DC50为 17.3 pM。PROTAC(H-PGDS)-7是一种类药化合物，能有效抑制前列腺素 D2 (PGD2)的产生，抑制炎症因子重生作用。PROTAC(H-PGDS)-7是治疗 DMD 和其他H-PGDS 相关疾病的候选化合物。

HPGDS inhibitor 2 (GSK-2894631A) 是高效的造血前列腺素 D 合成酶(H-PGDS)选择性抑制剂(IC50:9.9 nM)。

HQL-79 is a selective and orally active human hematopoietic prostaglandin D synthase (H-PGDS) inhibitor. It inhibits the synthesis of PGD2 and acts as an anti-allergic agent (Kd: 0.8 μM and IC50: 6 μM). It also shows no obvious effect on COX-1, COX-2, m-P

HPGDS inhibitor 1 是口服具有活性的HPGDS 选择性抑制剂，在酶和细胞分析中的IC50值分别为 0.6 nM 和 32 nM，但对 L-PGDS、mPGES、COX-1、COX-2 、5-LOX 无抑制作用。

TFC-007 是一种具有选择性和高效性的造血前列腺素 D 合成酶 (H-PGDS) 抑制剂，抑制炎症因子，可用于合成 H-PGDS 降解诱导剂 PROTAC (H-PGDS) -1 和研究雪松花粉诱导的豚鼠过敏性鼻炎。

hPGDS-IN-1是 hPGDS 抑制剂，使用荧光偏振检测或通过 EIA 法测得的 IC50值为12 nM。

Prostaglandin D2 (PGD2) is the major eicosanoid product of mast cells and is produced in large quantities by hematopoietic PGD synthase during allergic and asthmatic anaphylaxis. It causes vasodilation, flushing, hypotension, and is an inhibitor of platelet aggregation. Prostaglandin D2 methyl ester (PGD2 methyl ester) is a more lipid-soluble, cell-permeable prodrug form of PGD2. It binds to the human and mouse PGD2 receptors (DP1 and CRTH2 DP2) with 5-10 fold lower affinity than PGD2.

Prostaglandin D2 is synthesized by hematopoietic-type PGD-synthase (H-PGDS) in mast cells and is released in large quantities during allergic and asthmatic anaphylaxis. PGD2 is also produced in the brain by lipocalin-PGD-synthase also known as β-trace. In the brain, PGD2 produces normal physiological sleep and lowering of body temperature. Further pharmacological actions include inhibition of platelet aggregation and relaxation of vascular smooth muscle. tetranor-PGDM is a major metabolite of PGD2 that is detectable in human and mouse urine. The levels of tetranor-PGDM and 2,3-dinor-11β-PGF2α , a related PGD2 metabolite, in human urine were found to be 1.5 ± 0.3 and 0.6 ± ng mg creatinine, respectively. tetranor-PGDM was detected in murine urine at a level of 8.1 ± 1.3 ng mg creatinine.

TAS 205 is an inhibitor of hematopoietic prostaglandin D synthase (H-PGDS; IC50= 55.8 nM).1It is selective for H-PGDS over lipocalin-type PGDS (L-PGDS) at 100 μM, as well as over enzyme and receptor panels at 10 μM. TAS 205 inhibits production of prostaglandin D2induced by A23187 in KU812 human and RBL-2H3 rat basophils with IC50values of 78.3 and 181.3 nM, respectively. It inhibits ovalbumin-induced nasal lavage fluid eosinophil infiltration and late-phase nasal obstruction in an ovalbumin-sensitized guinea pig model of allergic rhinitis when administered at a dose of 30 mg kg. 1.Aoyagi, H., Kajiwara, D., Tsunekuni, K., et al.Potential synergistic effects of novel hematopoietic prostaglandin D synthase inhibitor TAS-205 and different types of anti-allergic medicine on nasal obstruction in a Guinea pig model of experimental allergic rhinitisEur. J. Pharmacol.875173030(2020)

HPGDS inhibitor 3 is a powerful oral compound that selectively inhibits the hematopoietic prostaglandin D synthase (H-PGDS). With an IC50 value of 9.4 nM and EC50 of 42 nM, it demonstrates high potency in peripherally restricting H-PGDS. Moreover, HPGDS inhibitor 3 exhibits excellent selectivity with no associated central nervous system toxicity. This compound also possesses favorable pharmacokinetic properties in mouse, rat, and dog models. Additionally, HPGDS inhibitor 3 displays noteworthy anti-inflammatory activity [1].

Prostaglandin D2 (PGD2) is a primary enzymatic prostaglandin derived from PGH2 and is abundantly produced in the cerebrospinal fluid (CSF) by the lipocalin-type PGD synthase, and peripherally by myeloid cells such as mast cells and basophils via a hematopoietic-type PGD synthase. PGD2 is chemically unstable and presents challenges for use and analysis due to its brief in vivo half-life. Δ12-PGD2, an initial decomposition product of PGD2, acts as an intermediate in the pathway to Δ12-PGJ2, a cyclopentenone prostaglandin known for its antimitotic and carcinogenic properties. The metabolism of Δ12-PGD2 involves the addition of thiol nucleophiles, a common pathway for many cyclopentenone prostaglandins.

PROTAC(H-PGDS)-8，一种针对造血前列腺素D合酶 (H-PGDS) 的PROTAC降解剂，具有 0.14 μM 的IC50值。