The company said OBI-3424 is a first-in-class novel small-molecule prodrug that selectively targets cancers overexpressing the enzyme aldo-keto reductase
1C3 (AKR1C3), and selectively releases a potent DNA alkylating agent in the presence of the AKR1C3 enzyme.
family 1 member B (AKR1B1) in chromosome 7 encodes a member of the aldo-keto reductase
superfamily, which consists of more than 40 known enzymes and proteins.
Role of aldo-keto reductase
family 1 (AKR1) enzymes in human steroid metabolism.
Horse GCLM protein possess the aldo-keto reductase
family domain which is covered by the amino acid sequences from 29 to 190 (Figure 1B).
Nevertheless, specific inhibition of aldose reductase with enzyme inhibitors is extremely challenging due to its extensive homology with other aldo-keto reductase
family members and makes it hard to find specific inhibitors that are devoid of properties to block other aldo-keto enzymes involved in protective physiological detoxification of toxic aldehydes formed within cells.
Within the group of overexpressed genes, the highest level of transcriptional activation was shown by enzymes that ensure vascular integrity, that is, serpin peptidase inhibitor and clade E (Serpine3), and the detoxification of metabolic products or environmental pollutants, that is, aldo-keto reductase
family-1, member E1 (Akr1e1).
In the study, using rats the team created a xenograft bladder cancer model, and discovered a three to 25-fold increase of the metabolic enzyme aldo-keto reductase
Because MG contains two functional groups (aldo- and keto-), it can be either oxidized or reduced by aldose/aldehyde reductase (ALR) or aldo-keto reductase
(AKR) using NADH or NADPH to form acetol, lactaldehyde and pyruvate (Kaur et al, 2014a, b; Hossain et al., 2016; Singh & Dhaka, 2016).
The second mechanism is attributed to the raised LH in patients with 17-[beta]-HSD3 deficiency, which in turn increases testicular testosterone production in patients with residual 17-[beta]-HSD3 function.[beta] In addition, the expression of aldo-keto reductase
family 1 member C3 (AKR1C3; 17-[beta]-HSD5) has been demonstrated in extragonadal tissues in response to high LH in both normal subjects and patients with 17-[beta]-HSD3 deficiency.
(17) reported that silencing of aldo-keto reductase
family 1, member C3 (AKR1C3) resulted in decreased expression of K10 but upregulation of loricrin, which is consistent with our results.
[PGF.sub.2[alpha]] is synthesized by enzymes of the aldo-keto reductase
(AKRs) family through various pathways [17,18].
UNDERSTANDING ALDO-KETO REDUCTASE
STEREOSELECTIVITY **, Timothy Simpson *, Brent Feske, Cliff Padgett and Scott C.