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Chemical compound
HL156A
Other names IM156, HL271 acetate, UNII-4G3BUV6ZSK
N'-[N'-[4-(trifluoromethoxy)phenyl]carbamimidoyl]pyrrolidine-1-carboximidamide
CAS Number
PubChem
CID
ChemSpider
UNII
CompTox Dashboard (
EPA )
Formula C 13 H 16 F 3 N 5 O
Molar mass 315.300 g·mol−1 3D model (
JSmol )
C1CCN(C1)C(=NC(=NC2=CC=C(C=C2)OC(F)(F)F)N)N
InChI=1S/C13H16F3N5O/c14-13(15,16)22-10-5-3-9(4-6-10)19-11(17)20-12(18)21-7-1-2-8-21/h3-6H,1-2,7-8H2,(H4,17,18,19,20)
Key:NGFUHJWVBKTNOE-UHFFFAOYSA-N
HL156A is a derivative of
metformin and a potent
oxidative phosphorylation inhibitor and
AMP-activated protein kinase activating biguanide.
[1]
[2] Certain types of cancer cells requires oxidative phosphorylation to survive. By targeting it, HL156A might help in improving anticancer therapy.
[3] It is more potent than
acadesine or metformin at activating AMP-activated protein kinase.
[2] It is synthesized by Hanall Biopharma.
[4]
Medical uses
It is in
phase 1 trial in patients with advanced solid tumor and
lymphoma .
[5]
[1]
Pharmacology
This section
is missing information about how the AMP-activated protein kinase effect translates to oxidative phosphorylation inhibition; whether these extra effects are downstream or independent of AMPK; whether a direct target is known (AMPK is not the direct target for metformin).
Please expand the section to include this information. Further details may exist on the
talk page . (July 2022 )
Apart from AMP-activated protein kinase activation, it also inhibits expression and activation of
insulin-like growth factor-1 ,
protein kinase B ,
mammalian target of rapamycin (mTOR), and
extracellular signal-regulated kinases .
[6]
[7]
Research
It is researched in multiple conditions like liver and renal
fibrosis ,
[2]
[8]
cancer
[6]
[9] and drug resistance in cancer.
[7] HL176OUT04, a drug with similar pharmacology, has been also developed.
[10]
See also
References
^
a
b Rha SY, Beom SH, Shin YG, Yim DS, Moon YW, Kim TW, et al. (2020). "Phase I study of IM156, a novel potent biguanide oxidative phosphorylation (OXPHOS) inhibitor, in patients with advanced solid tumors". Journal of Clinical Oncology . 38 (15_suppl): 3590.
doi :
10.1200/JCO.2020.38.15_suppl.3590 .
ISSN
0732-183X .
S2CID
219780562 .
^
a
b
c Tsogbadrakh B, Ju KD, Lee J, Han M, Koh J, Yu Y, et al. (2018).
"HL156A, a novel pharmacological agent with potent adenosine-monophosphate-activated protein kinase (AMPK) activator activity ameliorates renal fibrosis in a rat unilateral ureteral obstruction model" . PLOS ONE . 13 (8): e0201692.
Bibcode :
2018PLoSO..1301692T .
doi :
10.1371/journal.pone.0201692 .
PMC
6116936 .
PMID
30161162 .
^ Xu Y, Xue D, Bankhead A, Neamati N (December 2020).
"Why All the Fuss about Oxidative Phosphorylation (OXPHOS)?" . Journal of Medicinal Chemistry . 63 (23): 14276–14307.
doi :
10.1021/acs.jmedchem.0c01013 .
PMC
9298160 .
PMID
33103432 .
S2CID
225072329 .
^ Ju KD, Kim HJ, Tsogbadrakh B, Lee J, Ryu H, Cho EJ, et al. (March 2016).
"HL156A, a novel AMP-activated protein kinase activator, is protective against peritoneal fibrosis in an in vivo and in vitro model of peritoneal fibrosis" . American Journal of Physiology. Renal Physiology . 310 (5): F342–F350.
doi :
10.1152/ajprenal.00204.2015 .
PMID
26661649 .
^
"A Multi Center, Open-label, Phase 1 Clinical Trial to Evaluate the Safety, Tolerability, and Preliminary Efficacy of IM156 in Patients with Advanced Solid Tumors and Lymphoma" . 15 October 2020.
^
a
b Lam TG, Jeong YS, Kim SA, Ahn SG (March 2018).
"New metformin derivative HL156A prevents oral cancer progression by inhibiting the insulin-like growth factor/AKT/mammalian target of rapamycin pathways" . Cancer Science . 109 (3): 699–709.
doi :
10.1111/cas.13482 .
PMC
5834796 .
PMID
29285837 .
^
a
b Jeong YS, Lam TG, Jeong S, Ahn SG (August 2020).
"Metformin Derivative HL156A Reverses Multidrug Resistance by Inhibiting HOXC6/ERK1/2 Signaling in Multidrug-Resistant Human Cancer Cells" . Pharmaceuticals . 13 (9): 218.
doi :
10.3390/ph13090218 .
PMC
7560051 .
PMID
32872293 .
^ Lee HS, Shin HS, Choi J, Bae SJ, Wee HJ, Son T, et al. (October 2016).
"AMP-activated protein kinase activator, HL156A reduces thioacetamide-induced liver fibrosis in mice and inhibits the activation of cultured hepatic stellate cells and macrophages" . International Journal of Oncology . 49 (4): 1407–1414.
doi :
10.3892/ijo.2016.3627 .
PMID
27498767 .
^ Choi J, Lee JH, Koh I, Shim JK, Park J, Jeon JY, et al. (October 2016).
"Inhibiting stemness and invasive properties of glioblastoma tumorsphere by combined treatment with temozolomide and a newly designed biguanide (HL156A)" . Oncotarget . 7 (40): 65643–65659.
doi :
10.18632/oncotarget.11595 .
PMC
5323181 .
PMID
27582539 .
^ Hyeonsang S (2016).
The AMPK activators, HL156A and HL176OUT04 reduce thioacetamide-induced hepatic fibrosis via the inhibition of hepatic stellate cell activation (Ph.D. thesis). 서울대학교 융합과학기술대학원 (Seoul National University Graduate School of Convergence Science and Technology).
hdl :
10371/133411 .