Ligand Pharmaceuticals

Dr. Andrew Hudson Ligand Pharmaceuticals 10275 Science Center Road San Diego, CA 92121... 

Although no PPARS-specific ligands are currently FDA-approved, GW501516 is a compound being developed jointly by GlaxoSmithKline and Ligand Pharmaceuticals. This compound is currently in Phase II trials for the treatment of dyslipidemia. 

Agouron Pharmaceuticals. CytoGenix. Ligand Pharmaceuticals. SangStat... 

The major clinical study underpinning product approval was a randomized, double blind study in which 71 CTCL patients were administered the product at one of two dosage levels (9 or 18 [tg kg 1 day ) overall, 30 per cent of patients experienced an objective tumour response. Serious side effects potentially associated with product administration include acute hypersensitivity-type reactions, vascular leak syndrome and visual impairment. Additional adverse reactions include flu-like symptoms, headache, hyper- or hypo-tension, as well as digestive upset. Ontak is manufactured by Seragen Inc. and is distributed by Ligand Pharmaceuticals. 

Ontak Denileukin diftitox Ligand Pharmaceuticals 2/1999 Persistant or recurrent cutaneous T-cell lymphoma E. coli... 

Ligand Pharmaceuticals, San Diego, Emory University, Atlanta,... 

Liposomal daunorubicin (DaunoXome - Gilead) Denileukin diftitox (Ontak-Ligand Pharmaceuticals)... 

Dziewanowska, Zofia Ligand Pharmaceuticals Inc., 10275 Science Center Drive, SanDiego, CA 92121, USA. 

Figure 8.9 Quinolinone (pyridone) fused-ring SARMs from Ligand Pharmaceuticals, Inc.

Pfizer patented a series of AR ligands which are analogs of the Ligand Pharmaceuticals 6-quinolinone templates. These AR ligands are of three templates (i) 6-sulfonamide pyridones [132], (ii) benzyl urea pyridones [133] and (iii) benzyl coumarins [134] that appear to be weak affinity (micromolar) antagonists which are illustrated as representative examples 41, 42 and 43, respectively, in Figure 8.10. Conspicuously absent from these quinolinones is the aniline moiety, which may explain the low affinity and lack of agonist activity. 

Ligand Pharmaceuticals further extended their earlier SARM portfolio by eliminating the quinolinone A-ring from their bicydic template, leaving just the aniline. A variety of monoaryl ring systems (phenyl, naphthyl, indole) directly connected to a variety of acyclic (representative example 59 in Figure 8.11) and cyclic (example 60 in Figure 8.12) anilines [161] were reportedly SARMs, but no assays are described and no data reported for these compounds. 

SARMs of several structural templates and a variety of potencies are described in the peer-reviewed and patent literature, and the rate of publication is accelerating. Currently there are three groups that have produced clinical candidate SARMs GTx (Ostarine and andarine for cachexia and renal disease in phase II, structures not published), Bristol-Myers Squibb [BMS-564929 (102) (Figure 8.15) for age-related functional decline in phase I], and Ligand Pharmaceuticals [LGD2941 (40) for frailty and osteoporosis in phase I, and LGD2226 (39) which has been discontinued]. Not... 

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