Acelarin Logo

A ProTide Transformation of Gemcitabine

First-in-Class Nucleotide Analog

Acelarin has achieved impressive disease control rate and favourable tolerability in patients with advanced cancers


NuCana’s most advanced ProTide is comprised of a “pre-activated” nucleotide analog (gemcitabine monophosphate) and a protective phosphoramidate moiety, which is a specific combination of an aryl, ester and amino acid grouping.

This chemical structure profoundly changes the dynamic properties of the molecule, enabling Acelarin to enter the cancer cell independent of membrane transporters and protecting it from both extracellular and intracellular degradation.

Once Acelarin has entered the cancer cell, the moiety is optimally cleaved off, resulting in “deprotection” and the release of an activated, phosphorylated form of gemcitabine, dFdCMP. Accordingly, the activating enzyme, dCK, which drives the rate-limiting phosphorylation of gemcitabine, is no longer required and the cancer cells’ deficiency of dCK does not result in resistance to Acelarin, as it does with gemcitabine. The activated nucleotide analog, dFdCMP, is then rapidly converted to the diphosphate, dFdCDP, and then to the key anti-cancer triphosphate metabolite, dFdCTP. As a result, Acelarin achieves much higher intracellular levels of dFdCTP inside the patients’ cells than gemcitabine.

Animated acelarin Mode of Action (MOA)

Acelarin bypasses the key cancer resistance pathways of gemcitabine

Discover Acelarin Key Facts

Overcomes Resistance Mechanisms
50% Response Rate patients with biliary tract cancers (n=14)
93% Disease Control Rate patients with relapsed/refractory gynecological cancers (n=14)

217x higher intracellular levels of dFdCTP

Acelarin 217 higher graph

Acelarin Clinical Studies

Acelarin has been administered to over 230 patients with a wide range of advanced cancers. We are developing Acelarin for multiple indications: in both platinum-resistant and platinum-sensitive ovarian cancer; as first-line treatment in biliary cancer, an indication in which no drug has ever been approved; and as first-line treatment in pancreatic cancer. The National Cancer Research Institute in the UK is facilitating a Phase III study expected to enroll 328 patients with metastatic pancreatic cancer to compare Acelarin to gemcitabine as a first-line treatment. We announced in January 2018 that the 100th patient had been enrolled in this study.


Phase I dose-escalation study in patients with advanced solid tumours.
Discover More


Phase Ib study of Acelarin + carboplatin in patients with recurrent ovarian cancer.
Discover More


Phase Ib combination Acelarin + cisplatin in patients with locally advanced or metastatic biliary tract cancer.
Discover More


Phase III study comparing Acelarin with gemcitabine front line in patients with pancreatic cancer.

NuCana Ongoing or Planned Clinical Studies

ABC-08 - Phase Ib Study
in biliary tract cancer
NuTide:301 - Phase I Study
in advanced solid tumours
NuTide:701 - Phase I Study
in advanced solid tumours &
haematological malignancies
PRO-105 - Phase II Study
in platinum-resistant ovarian cancer
NuTide:302 - Phase Ib Study
in colorectal cancer
Acelarate - Phase III Study
in metastatic pancreatic carcinoma