. 2015 Jul 17;5(7):e325. doi: 10.1038/bcj.2015.46

Table 1. Pim inhibitors in development.

Drug	Class	Phase of development	Mechanism of action MM	Potency	Clinical trial identification	Condition	Status	Endpoint	Salient reports	Ref.
LGH447	3-S-aminopiperidine pyridyl carboxamide	Phase I/II	-Reduces p4EBP1, pS6K -Reduces pBAD -Cleave PARP and caspases 3,7,8,9 -Cell Cycle Arrest Go/G1	Ki Pim-1 5.8pM; Pim-2 18.0pM; Pim-3 9.3pM	NCT01456689	RRMM	Recruiting	MTD RDE	MTD 500 mg od ORR 10.5% CBR 21.1% DCR 71.9%	^{52, 53, 71}
					NCT02160951	RRMM	Recruiting	MTD RDE	Not reported at time of writing
					NCT02144038	RRMM, in combination with PI3K inhibitor BYL719	Recruiting	MTD RDE	Not reported at time of writing
					NCT02078609	AML/ high risk MDS	Recruiting	MTD	Not reported at time of wristing
AZD1208	Thiazolidene	Phase I (terminated)	-Reduces p4EBP1, pS6K -Reduces pBAD	IC50 <5 nM for each isoform	NCT01489722	AML	Terminated	MTD Efficacy	Not for further investigation owing to safety/efficacy issue	⁸²
					NCT01588548	Advanced lymphoma and solid organ malignancies	Completed	MTD
SGI-1776	Imidazopyridine	Phase I (terminated)	-Reduces p4EBP1, pS6K -Reduces pBAD -Autophagy	IC50 Pim-1 7 nM; Pim-2 363 nM; Pim-3 69 nM	NCT00848601	Refractory Prostate cancer/ RR NHL	Terminated	MTD PK PD	Terminated owing to cardiotoxicity	³⁹
					NCT01239108	RR Leukemia	Withdrawn	MTD	Terminated owing to cardiotoxicity
LGB321	3- S-aminopiperidine pyridyl carboxamide	Preclinical	-Reduces p4EBP1, pS6K -Reduces pBAD	Ki Pim-1 1pM; Pim-2.1pM; Pim-3 0.8pM	N/A		N/A	N/A	N/A	^{1, 16, 72}
AZD1897	Thiazolidene	Preclinical	-Reduces p4EBP1, pS6K	Data not available	N/A		N/A	N/A	N/A	⁷⁵

Abbreviations: AML, acute myeloid leukemia; CBR, clinical benefit rate; DCR, disease control rate; MTD, maximum tolerated dose; IC50, inhibitory concentration 50; Ki, inhibitory constant; MDS, myelodysplastic syndrome; ORR, overall response rate; RDE, recommended dose for expansion; RRMM, relapsed/refractory multiple myeloma; RR NHL, relapsed/refractory nonHodgkin lymphoma.