Table 1 The therapeutic protein kinase inhibiors in acute leukemia

FLT3

Quizartinib

An anti-FLT3 TKI, was investigated in ALL or AML

Nausea, anemia, vomiting, etc

I-II-III [70]

Midostaurin

It is an oral multi-targeted kinase inhibitor to inihibit leukemia cells including ALL and FLT3-positive AML

Diarhhoea, nausea, headache, etc.

I-II-III [71]

Sunitinib

Sunitinib inhibits leukemia cells survival and angiogenesis

Cardiotoxic, dyspnea, etc.

II [72]

Lestaurtinib

Lestaurtinib might inhibit the activity of FLT3 kinase and it is more appropriate during intensive chemotherapy

Gastrointestinal reaction, etc.

I-II-III [73]

Tandutinib

It inhibits the FLT3 ITD-positive rather than the ITD-negative patients with AML.

Bone pain, nausea, etc.

I-II-III

Gilteritinib

Gilteritinib is a kind of favourable safety agent and is being on trial at 120 mg/day

Diarrhea, etc.

I-II -III

Crenolanib

Crenolanib is a potential selective inhibitor of FLT3-ITDs and PDGFRα/β

Vomiting, headache, etc

II

Bortezomib

It is associated with apoptotic and autophagic cell death of AML

Gastro-intestinal, asthenia, etc

I-II-III [74]

BTK

Ibrutinib

Although ibrutinib has its own unique toxicity, it usually causes fewer infections

Pneumonia, sinusitis, headache upper respiratory tract infection, etc.

II

Acalabrutinib

It has received accelerated approval for the treatment of cell lymphoma

Headache, diarrhea, weight gain skin rash, severe diarrhea, etc.

I-II

JAK-STAT

Ruxolitinib

The JAK1/JAK2 inhibitor, is more effective against JAK-STAT pathway

Nausea, anemia, vomiting, ect.

III

Pacritinib (SB1518)

It is potent inhibitor FLT3-ITDs, JAK2, JAK2V617F in phase III development

Anemia, ect.

I-II-III [75]

Everolimus

Everolimus is combined with MK-2206, particularly important in the setting of resistance to therapeutic drugs

Cardiac failure, respiratory failure septic shock, etc.

I-II [76]

Temsirolimus

Temsirolimus combines with etoposide, cyclophosphamide and dexamethasone for relapsed pediatric ALL in adults

Nausea, etc.

I-II [77]

mTOR

Sirolimus

Sirolimus is an mTOR inhibitor, but it has a similar suppressive effect on the immune system

Abdominal pain, nausea, etc.

II [78]

AZD8055

AZD8055 inhibits the phosphorylation of mTORC1 with p70S6K and 4E–BP1 and downstream proteins

Anorexia, etc.

I

Ciclopirox

Ciclopirox enhances the effect of the preclinical antileukemia while irritation

Itching, blistering, swelling, etc.

I

MEK

Pimasertib

It is a novel, selective, orally bioavailable MEK1/2

Bleeding risk, etc.

II

GSK690693

It inhibits apoptosis in sensitive ALL cell lines

Not clearly

I

AKT

MK-2206

An orally inhibitor of the PI3K/Akt pathway which can inhibit tumor cell proliferation

Fatigue, vomiting, anorexia, etc

I-II

T315I

The mutation of T315I occurs to patients even when second- and third-genneration on trails

Nausea, swelling, rash, etc.

II-III

Gefitinib

A third-line agent and also is an EGFR inhibitor

Diarrhoea, vomiting, anorexia, etc.

II [79]

Ponatinib

It is a multi-targeted tyrosine-kinase inhibitor often with hypertension

Hypertension, rash, abdominal pain, fatigue, etc.

I-II

Bcr-Abl

Dasatinib

It also inhibits the Src kinase family

Anemia, diarrhea, swelling, rash, etc

II

ABL001

ABL001 is taken orally and the high does of it can be given safely to patients

Not clearly

I

BEZ235

BEZ-235 is a PI3K inhibitor. It also inhibits mTOR. It is being investigated as a possible leukemia treatment.

Anemia, vomiting, etc

I-II

PI3K

Idelalisib

Idelalisib is effective in leukemia patients who have p53 mutation

Fever, fatigue, nausea, cough abdominal, pain, rash, chills, etc.

on trial

PKI-587

Gedatolisib is an agent targeting the PI3K/mTOR pathway

Nausea, etc.

I

PLK1

Volasertib

It has been reported the volasertib inhibits PLK1 in both cancer and normal cells

Anaema, throm bocytopenia, nausea febrile neutropenia, etc.

I-II