NPASS Compound

Structure

NPC237219 OpenBabel07101719512D 36 39 0 0 1 0 0 0 0 0999 V2000 -1.7002 -1.5960 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.2605 5.8217 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.9662 5.5209 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.0586 0.6744 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 4.3247 -1.1352 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.3397 2.3508 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.4662 -0.9532 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.0000 2.7169 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8529 -0.4924 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.0265 5.1789 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.2926 0.0316 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 3.5586 -0.4924 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 3.2057 1.8508 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 -0.8529 3.2093 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8529 -1.4772 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.8529 4.1941 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -1.3529 0.3736 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 4.0586 2.3432 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -1.3529 2.3432 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.8529 -1.4772 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.5586 3.2093 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 4.0586 0.3736 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8529 4.1941 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.8529 -0.4924 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.7926 -1.1352 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 -0.0868 3.8521 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 -0.0868 -1.1352 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 2.7926 3.8521 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 -1.5265 1.3584 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 4.2323 1.3584 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 -2.2926 2.6853 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 2.0265 -2.4620 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 4.3247 3.8521 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 0.8529 3.2093 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 3.2057 0.8660 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 0.0000 0.0000 0.0000 S 0 0 0 0 0 0 0 0 0 0 0 0 1 7 1 0 0 0 0 2 10 1 0 0 0 0 3 10 1 0 0 0 0 7 11 1 0 0 0 0 8 14 2 0 0 0 0 8 34 1 0 0 0 0 9 15 2 0 0 0 0 9 36 1 0 0 0 0 11 4 1 6 0 0 0 12 5 1 6 0 0 0 12 22 1 0 0 0 0 12 25 1 0 0 0 0 13 6 1 6 0 0 0 13 18 1 0 0 0 0 13 35 1 0 0 0 0 14 19 1 0 0 0 0 14 26 1 0 0 0 0 15 20 1 0 0 0 0 15 27 1 0 0 0 0 16 10 1 6 0 0 0 16 23 1 0 0 0 0 16 28 1 0 0 0 0 17 11 1 1 0 0 0 17 24 1 0 0 0 0 17 29 1 0 0 0 0 18 21 1 1 0 0 0 18 30 1 0 0 0 0 19 29 2 3 0 0 0 19 31 1 0 0 0 0 20 25 2 3 0 0 0 20 32 1 0 0 0 0 21 28 2 3 0 0 0 21 33 1 0 0 0 0 22 30 2 0 0 0 0 22 35 1 0 0 0 0 23 26 2 0 0 0 0 23 34 1 0 0 0 0 24 27 2 0 0 0 0 24 36 1 0 0 0 0 M END $$$$

Physi-Chem Properties

Molecular Weight:	516.22
Volume:	496.783
LogP:	2.29
LogD:	3.254
LogS:	-2.786
# Rotatable Bonds:	3
TPSA:	158.9
# H-Bond Aceptor:	11
# H-Bond Donor:	4
# Rings:	4
# Heavy Atoms:	12

MedChem Properties

QED Drug-Likeness Score:	0.398
Synthetic Accessibility Score:	6.819
Fsp3:	0.542
Lipinski Rule-of-5:	Rejected
Pfizer Rule:	Accepted
GSK Rule:	Rejected
BMS Rule:	0
Golden Triangle Rule:	Rejected
Chelating Alert:	0
PAINS Alert:	0

ADMET Properties (ADMETlab2.0)

ADMET: Absorption

Caco-2 Permeability:	-5.363
MDCK Permeability:	1.5204462215478998e-05
Pgp-inhibitor:	0.001
Pgp-substrate:	0.998
Human Intestinal Absorption (HIA):	0.038
20% Bioavailability (F20%):	0.009
30% Bioavailability (F30%):	0.632

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.04
Plasma Protein Binding (PPB):	90.46627044677734%
Volume Distribution (VD):	2.944
Pgp-substrate:	6.804636001586914%

ADMET: Metabolism

CYP1A2-inhibitor:	0.167
CYP1A2-substrate:	0.239
CYP2C19-inhibitor:	0.242
CYP2C19-substrate:	0.081
CYP2C9-inhibitor:	0.397
CYP2C9-substrate:	0.047
CYP2D6-inhibitor:	0.002
CYP2D6-substrate:	0.111
CYP3A4-inhibitor:	0.213
CYP3A4-substrate:	0.575

ADMET: Excretion

Clearance (CL):	2.55
Half-life (T1/2):	0.239

ADMET: Toxicity

hERG Blockers:	0.03
Human Hepatotoxicity (H-HT):	0.997
Drug-inuced Liver Injury (DILI):	0.982
AMES Toxicity:	0.004
Rat Oral Acute Toxicity:	0.106
Maximum Recommended Daily Dose:	0.952
Skin Sensitization:	0.016
Carcinogencity:	0.368
Eye Corrosion:	0.003
Eye Irritation:	0.006
Respiratory Toxicity:	0.946

Download Data

Data Type	Select
General Info & Identifiers & Properties
Structure MOL file
Source Organisms
Biological Activities
Similar NPs/Drugs

Natural Product: NPC237219

Natural Product ID:	NPC237219
*Common Name:**	Aerucyclamide C
IUPAC Name:	n.a.
Synonyms:	Aerucyclamide C
Standard InCHIKey:	MQIAICAGVFTAAN-ZIYJYRAWSA-N
Standard InCHI:	InChI=1S/C24H32N6O5S/c1-7-11(4)17-24-27-15(9-36-24)20(32)25-12(5)22-30-18(13(6)35-22)21(33)28-16(10(2)3)23-26-14(8-34-23)19(31)29-17/h8-13,16-18H,7H2,1-6H3,(H,25,32)(H,28,33)(H,29,31)/t11-,12-,13+,16-,17+,18-/m0/s1
SMILES:	CC[C@H](C)[C@@H]1c2nc(cs2)C(=N[C@@H](C)C2=N[C@@H]([C@@H](C)O2)C(=N[C@@H](C(C)C)c2nc(co2)C(=N1)O)O)O
Synthetic Gene Cluster:	n.a.
ChEMBL Identifier:	CHEMBL575440
PubChem CID:	25156431
Chemical Classification:**	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000264] Organic acids and derivatives [CHEMONTID:0000265] Carboxylic acids and derivatives [CHEMONTID:0000013] Amino acids, peptides, and analogues [CHEMONTID:0000348] Peptides [CHEMONTID:0001995] Cyclic peptides

*Note: the InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
**Note: the Chemical Classification was calculated by NPClassifier Version 1.5. Reference: PMID:34662515.

Species Source

Organism ID	Organism Name	Taxonomy Level	Family	SuperKingdom	Isolation Part	Collection Location	Collection Time	Reference
NPO3288	Microcystis aeruginosa	Species	Microcystaceae	Bacteria	n.a.	n.a.	n.a.	PMID[11000050]
NPO3288	Microcystis aeruginosa	Species	Microcystaceae	Bacteria	n.a.	n.a.	n.a.	PMID[11374973]
NPO3288	Microcystis aeruginosa	Species	Microcystaceae	Bacteria	n.a.	n.a.	n.a.	PMID[12141855]
NPO3288	Microcystis aeruginosa	Species	Microcystaceae	Bacteria	n.a.	Einan Reservoir in Israel	n.a.	PMID[12141855]
NPO3288	Microcystis aeruginosa	Species	Microcystaceae	Bacteria	n.a.	n.a.	n.a.	PMID[18163584]
NPO3288	Microcystis aeruginosa	Species	Microcystaceae	Bacteria	n.a.	n.a.	n.a.	PMID[18558743]
NPO3288	Microcystis aeruginosa	Species	Microcystaceae	Bacteria	n.a.	n.a.	n.a.	PMID[18973386]
NPO3288	Microcystis aeruginosa	Species	Microcystaceae	Bacteria	water bloom of the cyanobacterium Microcystis aeruginosa	n.a.	n.a.	PMID[19650639]
NPO3288	Microcystis aeruginosa	Species	Microcystaceae	Bacteria	bloom material	Lake Kinneret, Israel	n.a.	PMID[22280481]
NPO3288	Microcystis aeruginosa	Species	Microcystaceae	Bacteria	n.a.	Kibbutz Geva, Israel	n.a.	PMID[23153007]
NPO3288	Microcystis aeruginosa	Species	Microcystaceae	Bacteria	n.a.	Water Reservoir near Kibbutz Hafetz Haim, Israel	n.a.	PMID[23718637]
NPO3288	Microcystis aeruginosa	Species	Microcystaceae	Bacteria	Bloom	n.a.	n.a.	PMID[24261937]
NPO3288	Microcystis aeruginosa	Species	Microcystaceae	Bacteria	n.a.	n.a.	n.a.	PMID[24642434]
NPO3288	Microcystis aeruginosa	Species	Microcystaceae	Bacteria	n.a.	n.a.	n.a.	PMID[24868986]
NPO3288	Microcystis aeruginosa	Species	Microcystaceae	Bacteria	n.a.	n.a.	n.a.	PMID[29405714]
NPO3288	Microcystis aeruginosa	Species	Microcystaceae	Bacteria	Bloom	n.a.	n.a.	PMID[29847132]
NPO3288	Microcystis aeruginosa	Species	Microcystaceae	Bacteria	n.a.	n.a.	n.a.	PMID[9249979]
NPO3288	Microcystis aeruginosa	Species	Microcystaceae	Bacteria	n.a.	n.a.	n.a.	PMID[9842728]
NPO3288	Microcystis aeruginosa	Species	Microcystaceae	Bacteria	n.a.	n.a.	n.a.	Database[Title]
NPO3288	Microcystis aeruginosa	Species	Microcystaceae	Bacteria	n.a.	n.a.	n.a.	Database[UNPD]

☑ Note for Reference:
In addition to directly collecting NP source organism data from primary literature (where reference will provided as NCBI PMID or DOI links), NPASS also integrated them from below databases:
☉ UNPD: Universal Natural Products Database [PMID: 23638153].
☉ StreptomeDB: a database of streptomycetes natural products [PMID: 33051671].
☉ TM-MC: a database of medicinal materials and chemical compounds in Northeast Asian traditional medicine [PMID: 26156871].
☉ TCM@Taiwan: a Traditional Chinese Medicine database [PMID: 21253603].
☉ TCMID: a Traditional Chinese Medicine database [PMID: 29106634].
☉ TCMSP: The traditional Chinese medicine systems pharmacology database and analysis platform [PMID: 24735618].
☉ HerDing: a herb recommendation system to treat diseases using genes and chemicals [PMID: 26980517].
☉ MetaboLights: a metabolomics database [PMID: 27010336].
☉ FooDB: a database of constituents, chemistry and biology of food species [www.foodb.ca].

NP Quantity Composition/Concentration

Organism ID	NP ID	Organism Material Preparation	Organism Part	NP Quantity (Standard)	NP Quantity (Minimum)	NP Quantity (Maximum)	Quantity Unit	Reference

☑ Note for Reference:
In addition to directly collecting NP quantitative data from primary literature (where reference will provided as NCBI PMID or DOI links), NPASS also integrated NP quantitative records for specific NP domains (e.g., NPS from foods or herbs) from domain-specific databases. These databases include:
☉ DUKE: Dr. Duke's Phytochemical and Ethnobotanical Databases.
☉ PHENOL EXPLORER: is the first comprehensive database on polyphenol content in foods [PMID: 24103452], its homepage can be accessed at here.
☉ FooDB: a database of constituents, chemistry and biology of food species [www.foodb.ca].

Biological Activity

Activity Type	# Activity
IC50	3
Others	1

Activity Type	# Activity
Cell Line	1
Organism	3

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT839	Cell Line	L6	Rattus norvegicus	IC50	=	106000.0	nM	PMID[452681]
NPT485	Organism	Plasmodium falciparum (isolate K1 / Thailand)	Plasmodium falciparum K1	IC50	=	2300.0	nM	PMID[452681]
NPT844	Organism	Trypanosoma brucei rhodesiense	Trypanosoma brucei rhodesiense	IC50	=	9200.0	nM	PMID[452681]
NPT6519	Organism	Thamnocephalus platyurus	Thamnocephalus platyurus	LC50	=	70500.0	nM	PMID[452681]

☑ Note for Activity Records:
☉ The quantitative biological activities were primarily integrated from ChEMBL (Version-30) database and were also directly collected from PubMed literature. PubMed PMID was provided as the reference link for each activity record.

Chemically structural similarity: I. Similar Active Natural Products in NPASS

Top-200 similar NPs were calculated against the active-NP-set (includes 4,3285 NPs with experimentally-derived bioactivity available in NPASS)

Similarity level is defined by Tanimoto coefficient (Tc) between two molecules. Tc lies between [0, 1] where '1' indicates the highest similarity. What is Tanimoto coefficient

● The left chart: Distribution of similarity level between NPC237219 and all remaining natural products in the NPASS database.
● The right table: Most similar natural products (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	332
0.1-0.2	13873
0.2-0.3	23805
0.3-0.4	4260
0.4-0.5	271
0.5-0.6	112
0.6-0.7	20
0.7-0.8	15
0.8-0.85	6
0.85-0.9	1
0.9-0.95	0
0.95-1	2

Similarity Score	Similarity Level	Natural Product ID
0.9524	High Similarity	NPC50274
0.8861	High Similarity	NPC256912
0.8553	High Similarity	NPC222391
0.8509	High Similarity	NPC34319
0.8428	Intermediate Similarity	NPC110129
0.8428	Intermediate Similarity	NPC201014
0.8239	Intermediate Similarity	NPC217981
0.7905	Intermediate Similarity	NPC89592
0.7755	Intermediate Similarity	NPC51692
0.7582	Intermediate Similarity	NPC74917
0.7532	Intermediate Similarity	NPC120917
0.7432	Intermediate Similarity	NPC135558
0.74	Intermediate Similarity	NPC267605
0.7391	Intermediate Similarity	NPC475390
0.7297	Intermediate Similarity	NPC214375
0.7125	Intermediate Similarity	NPC103268
0.6989	Remote Similarity	NPC164006
0.6796	Remote Similarity	NPC132662
0.6782	Remote Similarity	NPC235866
0.645	Remote Similarity	NPC469801
0.6444	Remote Similarity	NPC475554
0.6369	Remote Similarity	NPC56058
0.6369	Remote Similarity	NPC522
0.6359	Remote Similarity	NPC134480
0.6324	Remote Similarity	NPC473704
0.6257	Remote Similarity	NPC476080
0.6257	Remote Similarity	NPC475534
0.6257	Remote Similarity	NPC161242
0.6223	Remote Similarity	NPC475330
0.6222	Remote Similarity	NPC216720
0.619	Remote Similarity	NPC174652
0.619	Remote Similarity	NPC25316
0.619	Remote Similarity	NPC229160
0.619	Remote Similarity	NPC263485
0.6188	Remote Similarity	NPC210424
0.6089	Remote Similarity	NPC315872
0.602	Remote Similarity	NPC329961
0.602	Remote Similarity	NPC122427
0.5966	Remote Similarity	NPC319751
0.596	Remote Similarity	NPC165538
0.5936	Remote Similarity	NPC24990
0.5911	Remote Similarity	NPC476829
0.5904	Remote Similarity	NPC476103
0.5876	Remote Similarity	NPC314523
0.5876	Remote Similarity	NPC58001
0.5866	Remote Similarity	NPC119481
0.5816	Remote Similarity	NPC96016
0.581	Remote Similarity	NPC473398
0.5762	Remote Similarity	NPC475350
0.5762	Remote Similarity	NPC145178
0.5762	Remote Similarity	NPC14877
0.5697	Remote Similarity	NPC315411
0.5694	Remote Similarity	NPC49195
0.5684	Remote Similarity	NPC30527
0.5681	Remote Similarity	NPC251036
0.5631	Remote Similarity	NPC107458
0.5631	Remote Similarity	NPC295653

Chemically structural similarity: II. Similar Clinical/Approved Drugs

Similarity level is defined by Tanimoto coefficient (Tc) between two molecules.

● The left chart: Distribution of similarity level between NPC237219 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	133
0.1-0.2	1471
0.2-0.3	4699
0.3-0.4	2581
0.4-0.5	226
0.5-0.6	38
0.6-0.7	2
0.7-0.8	0
0.8-0.85	0
0.85-0.9	0
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Drug ID	Developmental Stage
0.6313	Remote Similarity	NPD7896	Approved
0.6089	Remote Similarity	NPD6444	Clinical (unspecified phase)
0.5988	Remote Similarity	NPD9579	Approved
0.5904	Remote Similarity	NPD2623	Phase 1
0.5871	Remote Similarity	NPD6347	Phase 2
0.5803	Remote Similarity	NPD2957	Phase 2
0.5764	Remote Similarity	NPD7490	Discontinued
0.5629	Remote Similarity	NPD2225	Clinical (unspecified phase)

Bioactivity similarity: Similar Natural Products in NPASS

Bioactivity similarity was calculated based on bioactivity descriptors of compounds. The bioactivity descriptors were calculated by a recently developed AI algorithm Chemical Checker (CC) [Nature Biotechnology, 38:1087–1096, 2020; Nature Communications, 12:3932, 2021], which evaluated bioactivity similarities at five levels:
☉ A: chemistry similarity;
☉ B: biological targets similarity;
☉ C: networks similarity;
☉ D: cell-based bioactivity similarity;
☉ E: similarity based on clinical data.

Those 5 categories of CC bioactivity descriptors were calculated and then subjected to manifold projection using UMAP algorithm, to project all NPs on a 2-Dimensional space. The current NP was highlighted with a small circle in the 2-D map. Below figures: left-to-right, A-to-E.

A: chemistry similarity

B: biological targets similarity

C: networks similarity

D: cell-based bioactivity similarity

E: similarity based on clinical data