更新于：2024-11-01

ALDH1A2 x ALDH1A1

更新于：2024-11-01

基本信息

关联

项与 ALDH1A2 x ALDH1A1 相关的药物

ABD-3001

靶点

ALDH1A1 x ALDH1A2

作用机制

ALDH1A1抑制剂 [+1]

在研机构

Advanced BioDesign SAS [+2]

原研机构

Advanced BioDesign SAS

在研适应症

成人急性髓性白血病 [+8]

非在研适应症-

最高研发阶段临床1期

首次获批国家/地区-

首次获批日期1800-01-20

项与 ALDH1A2 x ALDH1A1 相关的临床试验

NCT05601726 / Recruiting临床1期

First-In-Human, Open Label, Dose Escalation Study to Evaluate Safety, PK and PD of ABD-3001 as Monotherapy in Relapsed/Refractory Acute Myeloid Leukemia or High/Very-high Risk Myelodysplastic Syndromes Patients, Ineligible for Intensive or New Generation Targeted Therapy.

This First In Human (FIH) study is a prospective, open-label, multicenter, Phase 1 study, with a dose escalation design, followed by an optimized design. It will consist in a Single Ascending Dose (SAD) part and a Multiple Ascending Dose (MAD) part followed by a "Regimen optimization" part with an extension cohort.

开始日期2022-11-08

申办/合作机构

Advanced BioDesign SAS

100 项与 ALDH1A2 x ALDH1A1 相关的临床结果

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100 项与 ALDH1A2 x ALDH1A1 相关的转化医学

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0 项与 ALDH1A2 x ALDH1A1 相关的专利（医药）

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140

项与 ALDH1A2 x ALDH1A1 相关的文献（医药）

2024-06-28·ACTA HISTOCHEMICA ET CYTOCHEMICA

Expression of Retinaldehyde Dehydrogenases in the Pituitary Glands of Fetus and Adult Mice

Article

作者: Fujiwara, Ken ; Tsukada, Takehiro ; Cheng, Si ; Horiguchi, Kotaro ; Wei, Yanan ; Fujiwara, Yoko

Retinoic acid (RA) plays a critical role in cell growth and tissue development. RA is synthesized from retinoids through oxidation processes by the retinaldehyde dehydrogenase (Raldh) family. However, the expression of Raldhs during pituitary development and the identification of Raldh-expressing cells in the adult pituitary have not been fully elucidated. Here, we performed in situ hybridization to localize the three Raldh isoforms (Raldh1-3) in fetal and adult mouse pituitary glands. The results showed that Raldh2 expression was observed in Rathke's pouch from embryonic day 13.5 (E13.5), and this expression was sustained in the anterior lobe of the pituitary primordium from E15.5 to E17.5. In contrast, Raldh1 and Raldh3 were rarely detectable. Real-time PCR analysis revealed that Raldh2 was the predominant isoform expressed in the adult pituitary, although Raldh1 was also expressed to a lesser extent. In the adult pituitary, Raldh1-expressing cells were primarily observed in the posterior lobe. Raldh2-expressing cells were found in the marginal cell layer and parenchyma of the anterior lobe and were immunopositive for aldolase C (folliculostellate cells), but not for anterior pituitary hormones. These results suggest that RA is an important regulatory factor in the functions of the pituitary throughout its development in mice.

2024-04-01·Journal of Advanced Research

Retinoic acid enhances ovarian steroidogenesis by regulating granulosa cell proliferation and MESP2/STAR/CYP11A1 pathway

Article

作者: Wang, Huakai ; Li, Jie ; Wang, Xinyu ; Zhu, Zhekun ; Zeng, Xiangfang ; Zeng, Xiangzhou ; Chen, Meixia ; Cai, Shuang ; Xue, Bangxin ; Qiao, Shiyan

INTRODUCTIONOvarian steroidogenesis not only affects the embryonic development and pregnancy outcome, but also associates with many diseases in mammals and women. Exploring the nutrients and mechanisms influencing ovarian steroidogenesis is critical to maintaining the optimal reproductive performance, as well as guaranteeing body health.OBJECTIVESThis research aimed to explore the effect of retinol metabolism on ovarian steroidogenesis and the underlying mechanisms.METHODSComparative transcriptomic analysis of ovaries from normal and low reproductive performance sows were performed to identify the main causes leading to low fertility. The metabolites regulating steroid hormones synthesis were investigated in ovarian granulosa cells. Gene interference, overexpression, dual-luciferase reporter assays, chromatin immunoprecipitation and transcriptome analysis were further conducted to explore the underlying mechanisms of Aldh1a1 mediating ovarian steroidogenesis.RESULTSTranscriptome analysis of ovaries from normal and low reproductive performance sows showed the significant differences in both retinol metabolism and steroid hormones synthesis, indicating retinol metabolism probably influenced steroid hormones synthesis. The related metabolite retinoic acid was furtherly proven a highly active and potent substance strengthening estrogen and progesterone synthesis in ovarian granulosa cells. For the first time, we revealed that retinoic acid synthesis in porcine and human ovarian granulosa cells was dominated by Aldh1a1, and required the assistance of Aldh1a2. Importantly, we demonstrated that Aldh1a1 enhanced the proliferation of ovarian granulosa cells by activating PI3K-Akt-hedgehog signaling pathways. In addition, Aldh1a1 regulated the expression of transcription factor MESP2, which targeted the transcription of Star and Cyp11a1 through binding to corresponding promoter regions.CONCLUSIONOur data identified Aldh1a1 modulates ovarian steroidogenesis through enhancing granulosa cell proliferation and MESP2/STAR/CYP11A1 pathway. These findings provide valuable clues for improving ovarian health in mammals.

2024-02-02·Cancer Immunology Research

RALDH1 Inhibition Shows Immunotherapeutic Efficacy in Hepatocellular Carcinoma

Article

作者: Zhai, Li ; Furth, Emma E ; Simeonov, Anton ; Simon, M Celeste ; Zakharov, Alexey V ; Molina Arocho, William A ; Yu, Pengfei ; Haldar, Malay ; Mohei, Hesham ; Rai, Ganesha ; Yang, Shyh-Ming ; Scott, Alexis L ; Cao, Shuwen ; Yasgar, Adam ; Lobel, Graham P ; Martinez, Natalia J

AbstractGlobally, hepatocellular carcinoma (HCC) is one of the most commonly diagnosed cancers and a leading cause of cancer-related death. We previously identified an immune evasion pathway whereby tumor cells produce retinoic acid (RA) to promote differentiation of intratumoral monocytes into protumor macrophages. Retinaldehyde dehydrogenase 1 (RALDH1), RALDH2, and RALDH3 are the three isozymes that catalyze RA biosynthesis. In this study, we have identified RALDH1 as the key driver of RA production in HCC and demonstrated the efficacy of RALDH1-selective inhibitors (Raldh1-INH) in suppressing RA production by HCC cells. Raldh1-INH restrained tumor growth in multiple mouse models of HCC by reducing the number and tumor-supporting functions of intratumoral macrophages as well as increasing T-cell infiltration and activation within tumors. Raldh1-INH also displayed favorable pharmacokinetic, pharmacodynamic, and toxicity profiles in mice thereby establishing them as promising new drug candidates for HCC immunotherapy.