DEVELOPING DERMATOLOGY ASSETS IN THE COSMETIC AND DRUG SPACE
Isoprenylcysteine (IPC) analogs are a novel technology platform with broad utility over multiple inflammatory dermatological conditions. Signum’s approach is to develop small molecules that modulate G-protein-mediated and toll-like receptor-mediated signal transduction to achieve substantial therapeutic relief and/or provide anti-inflammatory and anti-aging protection to the skin.
IPC analogs were initially discovered by Dr. Jeffry B. Stock (co-founder of Signum Biosciences), in the course of an investigation of the chemistry that regulates the targeting of intracellular signal transduction G-proteins such as Ras, Rho, Rac, and GY. N-acetyl-S-farnesyl-L-cysteine (AFC), (trademark name Arazine™,) a small molecule IPC analog has been identified as a potential archetype of a novel class of safe, topical anti-inflammatories IPC analogs contain a 15- or 20-carbon side chain attached to the amino acid cysteine, mimicking the C-terminus of G-proteins.
These small molecules inhibit signaling activation in the membrane, by competing with isoprenoid groups for prenyl-binding sites of interaction at the membrane. Moreover, IPC analogs disrupt signal transduction by inhibiting heterotrimeric G-protein formation and/or by modulating different GPCRs. Furthermore, recent studies have demonstrated IPC analogs also modulate toll-like receptor (TLR) signaling, which play a key role in the innate immune response in skin (see SID posters in the News section).
Signum’s medicinal chemistry and screening efforts have yielded 2nd generation IPC compounds with increased potency against key pro-inflammatory cytokines that contribute to the pathogenesis of several skin diseases (SIG990 (DMT200/DMT210) – Rx lead for rosacea has been out-licensed to Dermata Therapeutics; SIG1451 – Rx lead for atopic dermatitis), highlighting the strong potential of this new class of anti-inflammatory compounds. Furthermore, in addition to Arazine™, we have developed new cosmeceutical functional ingredients (CFI), SIG-1273 to combat skin aging andSIG-1191, which targets inflammation and skin hydration.
Our latest CFIs, SIG-1459 and SIG-1460 are being developed to target the appearance of acne and troubled skin.