1.3 Hypomethylating agents and stuff med chem

SU bffr

hypomethylating agents treat ___ malignancies by inhibiting DNA methylation

hematological

hypomethylating agents MOA

prevent DNA nucleotides from being modified by adding a methyl group

They also activate genes that help cells mature and kill cells that are dividing rapidly.

hypomethylating agents prevent DNA nucleotides from being modified by…

adding a methyl group

hypomethylating agents activate genes that…

help cells mature and kill cells that are dividing rapidly

how do hypomethylating agents work

turn on genes that were off

when are hypomethylating agents used?

acute myeloid leukemia, MDA, other leukemias

cytidine class

hypomethylating agent

azacitidine class

hypomethylating agent

decitabine class

hypomethylating

azacitidine efficacy is likely due to….

RNA dependent effects

Azacitidine gets incorporated into RNA and can inhibit ___

tRNA methylation

how does Azacitidine inhibit tRNA methylation?

reduces tRNA methyltransferase levels

Azacitidine disrupts ____processes which leads to apoptosis

rRNA

Azacitidine can undergo spontaneous _____ and _____ by cytdine deaminase

hydrolysis and deamination

Decitabine at low doses impairs DNA methylation by…

irreversible inhibition of DNA methyltransferases (DNMT1)

DNMT1 recognizes Decitabine and it becomes ___ bound

irreversibly

when Decitabine and DNMT1 become bound it leads to…

methylation marks becoming lost during replication, whcih can lead to reactivation of silenced tumor suppressor geness

Decitabine is ____ potent than azacitidine

more

Decitabine is dif from azacitidine in MOA bc it is…

S-phase specific

Cisplatin is in ___ config

cis

Cisplatin contains ___ atom that acts as a magnet for electron rich DNA nucleophiles

electron deficient metal

Cisplatin reactivity with _________ is much faster than its metabolic reactions.

cellular nucleophiles or H2O

Cisplatin should not be refrigerated bc…

it will precipitate out

Cisplatin should never be given with needles or IV sets containing __ bc it leads to precipitation and loss of activity

aluminium

platinum containing products can lead to ___ damage

renal

to avoid kidney damage by platinum agents pts should…

drink water with chloride in it or try sodium thiosulfate

after platinum is admin, it tightly binds to which plasma proteins

albumin, transferrin, adn gamma-globulin

Carboplatin is similar to cisplatin except there is a ….

cyclobutane group instead of 2 Cl

Carboplatin, made with a cyclobutane instead of two Cl allows for…

anticancer activity

slower reaction rates

decreased potency

Advantages of carboplatin over cisplatin?

which has less SE (nephrotoxic ones)

carboplatin

Advantages of carboplatin over cisplatin?

which one has less binding to plasma proteins and improved stability

carboplatin

Advantages of carboplatin over cisplatin?

which one stays in the blood for longer times

carboplatin

Advantages of carboplatin over cisplatin?

which one has longer half life

carboplatin

Advantages of carboplatin over cisplatin?

which one causes myelosuppression

carboplatin

Advantages of carboplatin over cisplatin?

which one is more potent

cisplatin