Identification of the mechanism of action of CYT-0851, an inhibitor of monocarboxylate transporter (MCT) mediated lactate transport

B. Bradley; M. A. Belmonte; S. Kansara; J. L. Blank; L. Cryan; N. M. Reilly; V. Murali; D. H. Miller; J. P. Secrist

doi:10.1016/S0959-8049(22)00868-1

Identification of the mechanism of action of CYT-0851, an inhibitor of monocarboxylate transporter (MCT) mediated lactate transport

B. Bradley
, M. A. Belmonte
, S. Kansara
, J. L. Blank
, L. Cryan
, N. M. Reilly
, V. Murali
, D. H. Miller
, J. P. Secrist

Cyteir Therapeutics

Allbwn ymchwil: Cyfraniad at gyfnodolyn › Erthygl › adolygiad gan gymheiriaid

Crynodeb

CYT-0851 was discovered using a phenotypic screen and rapidly advanced to a phase 1 clinical trial where responses in solid tumor and lymphoma patients have been observed. To elucidate the mechanism of action (MOA) of CYT-0851, extensive bioinformatic, functional genomic, and molecular characterization was performed. This preclinical work demonstrated that CYT-0851 disrupts lactate transport via inhibition of monocarboxylate transporter (MCT) activity. In rapidly proliferating cancers, lactate is produced during glycolysis and is exported primarily by MCT1 and MCT4, which provide functional redundancy when co-expressed.

Iaith wreiddiol	Anadnabyddus
Tudalennau (o-i)	S24-S25
Cyfnodolyn	European Journal of Cancer
Cyfrol	174
Rhif cyhoeddi	1
Dyddiad ar-lein cynnar	28 Hyd 2022
Dynodwyr Gwrthrych Digidol (DOIs)	https://doi.org/10.1016/S0959-8049(22)00868-1
Statws	E-gyhoeddi cyn argraffu - 28 Hyd 2022
Cyhoeddwyd yn allanol	Ie

NDC y CU

Mae’r allbwn hwn yn cyfrannu at y Nod(au) Datblygu Cynaliadwy canlynol

NDC 3 Iechyd a Llesiant Da

Mynediad at Ddogfen

10.1016/S0959-8049(22)00868-1

Dyfynnu hyn

Bradley, B., Belmonte, M. A., Kansara, S., Blank, J. L., Cryan, L., Reilly, N. M., Murali, V., Miller, D. H., & Secrist, J. P. (2022). Identification of the mechanism of action of CYT-0851, an inhibitor of monocarboxylate transporter (MCT) mediated lactate transport. European Journal of Cancer, 174(1), S24-S25. Cyhoeddiad ar-lein ymlaen llaw. https://doi.org/10.1016/S0959-8049(22)00868-1

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title = "Identification of the mechanism of action of CYT-0851, an inhibitor of monocarboxylate transporter (MCT) mediated lactate transport",

abstract = "CYT-0851 was discovered using a phenotypic screen and rapidly advanced to a phase 1 clinical trial where responses in solid tumor and lymphoma patients have been observed. To elucidate the mechanism of action (MOA) of CYT-0851, extensive bioinformatic, functional genomic, and molecular characterization was performed. This preclinical work demonstrated that CYT-0851 disrupts lactate transport via inhibition of monocarboxylate transporter (MCT) activity. In rapidly proliferating cancers, lactate is produced during glycolysis and is exported primarily by MCT1 and MCT4, which provide functional redundancy when co-expressed.",

author = "B. Bradley and Belmonte, \{M. A.\} and S. Kansara and Blank, \{J. L.\} and L. Cryan and Reilly, \{N. M.\} and V. Murali and Miller, \{D. H.\} and Secrist, \{J. P.\}",

year = "2022",

month = oct,

day = "28",

doi = "10.1016/S0959-8049(22)00868-1",

language = "Anadnabyddus",

volume = "174",

pages = "S24--S25",

journal = "European Journal of Cancer",

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TY - JOUR

T1 - Identification of the mechanism of action of CYT-0851, an inhibitor of monocarboxylate transporter (MCT) mediated lactate transport

AU - Bradley, B.

AU - Belmonte, M. A.

AU - Kansara, S.

AU - Blank, J. L.

AU - Cryan, L.

AU - Reilly, N. M.

AU - Murali, V.

AU - Miller, D. H.

AU - Secrist, J. P.

PY - 2022/10/28

Y1 - 2022/10/28

N2 - CYT-0851 was discovered using a phenotypic screen and rapidly advanced to a phase 1 clinical trial where responses in solid tumor and lymphoma patients have been observed. To elucidate the mechanism of action (MOA) of CYT-0851, extensive bioinformatic, functional genomic, and molecular characterization was performed. This preclinical work demonstrated that CYT-0851 disrupts lactate transport via inhibition of monocarboxylate transporter (MCT) activity. In rapidly proliferating cancers, lactate is produced during glycolysis and is exported primarily by MCT1 and MCT4, which provide functional redundancy when co-expressed.

AB - CYT-0851 was discovered using a phenotypic screen and rapidly advanced to a phase 1 clinical trial where responses in solid tumor and lymphoma patients have been observed. To elucidate the mechanism of action (MOA) of CYT-0851, extensive bioinformatic, functional genomic, and molecular characterization was performed. This preclinical work demonstrated that CYT-0851 disrupts lactate transport via inhibition of monocarboxylate transporter (MCT) activity. In rapidly proliferating cancers, lactate is produced during glycolysis and is exported primarily by MCT1 and MCT4, which provide functional redundancy when co-expressed.

U2 - 10.1016/S0959-8049(22)00868-1

DO - 10.1016/S0959-8049(22)00868-1

M3 - Erthygl

SN - 0959-8049

VL - 174

SP - S24-S25

JO - European Journal of Cancer

JF - European Journal of Cancer

IS - 1

ER -