NPASS Compound

Structure

NPC120917 OpenBabel07101719252D 50 55 0 0 1 0 0 0 0 0999 V2000 3.2820 -2.8452 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 4.9096 -2.2528 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -8.0131 0.0258 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.6863 -1.0875 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.0574 -1.2779 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.6418 0.8707 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.5827 -1.1394 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.3855 0.6182 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.3116 0.6477 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.8823 -1.3454 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.6913 -1.8404 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.1938 0.9810 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.9248 -2.0791 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.0283 -0.1478 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.5574 -2.1439 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 -3.0725 1.6928 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 2.5979 -0.9658 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 -5.4007 0.4446 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 1.7404 1.3904 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.3384 -2.2161 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.4831 -2.4512 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 -0.7290 1.8258 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 0.9862 -2.8866 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -3.4924 2.5815 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 0.9862 1.8258 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.4387 -2.6527 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.7404 -2.4512 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.3830 2.1266 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.7290 -2.8866 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.5331 2.4202 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.5979 -0.0950 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.3904 -0.5554 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.3001 -1.7841 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 -5.0491 1.3807 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 0.1286 1.9770 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 -2.4421 -2.7347 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 2.3001 0.7233 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 -5.0196 -1.4841 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 0.1286 -3.0378 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 -2.4977 2.6840 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 1.3282 2.7655 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.7025 -3.6172 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 2.3831 -3.2172 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.9938 2.9184 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.3002 -2.1439 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.0928 1.6121 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 1.7404 -0.0950 0.0000 S 0 0 0 0 0 0 0 0 0 0 0 0 -4.4083 -0.5150 0.0000 S 0 0 0 0 0 0 0 0 0 0 0 0 -0.1736 -0.9848 0.0000 S 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 13 1 0 0 0 0 2 13 1 0 0 0 0 3 14 1 0 0 0 0 4 14 1 0 0 0 0 7 13 1 0 0 0 0 8 14 1 0 0 0 0 9 19 2 0 0 0 0 9 47 1 0 0 0 0 10 20 2 0 0 0 0 10 48 1 0 0 0 0 11 49 1 0 0 0 0 12 50 1 0 0 0 0 15 5 1 6 0 0 0 15 23 1 0 0 0 0 15 45 1 0 0 0 0 16 6 1 6 0 0 0 16 24 1 0 0 0 0 16 46 1 0 0 0 0 17 7 1 1 0 0 0 17 31 1 0 0 0 0 17 33 1 0 0 0 0 18 8 1 1 0 0 0 18 32 1 0 0 0 0 18 34 1 0 0 0 0 19 25 1 0 0 0 0 19 37 1 0 0 0 0 20 26 1 0 0 0 0 20 38 1 0 0 0 0 21 11 1 6 0 0 0 21 29 1 0 0 0 0 21 36 1 0 0 0 0 22 12 1 6 0 0 0 22 30 1 0 0 0 0 22 35 1 0 0 0 0 23 27 1 1 0 0 0 23 39 1 0 0 0 0 24 28 1 1 0 0 0 24 40 1 0 0 0 0 25 35 2 3 0 0 0 25 41 1 0 0 0 0 26 36 2 3 0 0 0 26 42 1 0 0 0 0 27 33 2 3 0 0 0 27 43 1 0 0 0 0 28 34 2 3 0 0 0 28 44 1 0 0 0 0 29 39 2 0 0 0 0 29 45 1 0 0 0 0 30 40 2 0 0 0 0 30 46 1 0 0 0 0 31 37 2 0 0 0 0 31 47 1 0 0 0 0 32 38 2 0 0 0 0 32 48 1 0 0 0 0 49 50 1 0 0 0 0 M END $$$$

Physi-Chem Properties

Molecular Weight:	762.21
Volume:	699.076
LogP:	3.152
LogD:	4.116
LogS:	-1.699
# Rotatable Bonds:	4
TPSA:	203.43
# H-Bond Aceptor:	14
# H-Bond Donor:	5
# Rings:	6
# Heavy Atoms:	18

MedChem Properties

QED Drug-Likeness Score:	0.178
Synthetic Accessibility Score:	4.478
Fsp3:	0.594
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:	-4.755
MDCK Permeability:	1.5039493518997915e-05
Pgp-inhibitor:	0.019
Pgp-substrate:	0.999
Human Intestinal Absorption (HIA):	0.016
20% Bioavailability (F20%):	0.007
30% Bioavailability (F30%):	0.01

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.977
Plasma Protein Binding (PPB):	55.53378677368164%
Volume Distribution (VD):	3.296
Pgp-substrate:	19.395488739013672%

ADMET: Metabolism

CYP1A2-inhibitor:	0.084
CYP1A2-substrate:	0.043
CYP2C19-inhibitor:	0.088
CYP2C19-substrate:	0.063
CYP2C9-inhibitor:	0.156
CYP2C9-substrate:	0.027
CYP2D6-inhibitor:	0.002
CYP2D6-substrate:	0.034
CYP3A4-inhibitor:	0.058
CYP3A4-substrate:	0.832

ADMET: Excretion

Clearance (CL):	2.276
Half-life (T1/2):	0.11

ADMET: Toxicity

hERG Blockers:	0.004
Human Hepatotoxicity (H-HT):	1.0
Drug-inuced Liver Injury (DILI):	0.996
AMES Toxicity:	0.007
Rat Oral Acute Toxicity:	0.097
Maximum Recommended Daily Dose:	0.989
Skin Sensitization:	0.096
Carcinogencity:	0.036
Eye Corrosion:	0.003
Eye Irritation:	0.007
Respiratory Toxicity:	0.682

Download Data

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

Natural Product: NPC120917

Natural Product ID:	NPC120917
*Common Name:**	Ulithiacyclamide
IUPAC Name:	n.a.
Synonyms:	Ulithiacyclamide
Standard InCHIKey:	FSUFGKVPTHSJKC-OFGHLPPXSA-N
Standard InCHI:	InChI=1S/C32H42N8O6S4/c1-13(2)7-17-31-37-19(9-47-31)25(41)35-22-12-50-49-11-21(29-39-23(15(5)45-29)27(43)33-17)36-26(42)20-10-48-32(38-20)18(8-14(3)4)34-28(44)24-16(6)46-30(22)40-24/h9-10,13-18,21-24H,7-8,11-12H2,1-6H3,(H,33,43)(H,34,44)(H,35,41)(H,36,42)/t15-,16-,17-,18-,21-,22-,23+,24+/m1/s1
SMILES:	CC(C)C[C@@H]1c2nc(cs2)C(=N[C@@H]2CSSC[C@H](C3=N[C@@H]([C@@H](C)O3)C(=N1)O)N=C(c1csc([C@@H](CC(C)C)N=C([C@@H]3[C@@H](C)OC2=N3)O)n1)O)O
Synthetic Gene Cluster:	n.a.
ChEMBL Identifier:	CHEMBL502961
PubChem CID:	44593594
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
NPO4712	Lissoclinum patella	Species	Didemnidae	Eukaryota	n.a.	n.a.	n.a.	PMID[1593285]
NPO4712	Lissoclinum patella	Species	Didemnidae	Eukaryota	n.a.	n.a.	n.a.	PMID[2095371]
NPO4712	Lissoclinum patella	Species	Didemnidae	Eukaryota	n.a.	n.a.	n.a.	PMID[2809606]
NPO4712	Lissoclinum patella	Species	Didemnidae	Eukaryota	n.a.	n.a.	n.a.	PMID[7623037]
NPO4712	Lissoclinum patella	Species	Didemnidae	Eukaryota	n.a.	n.a.	n.a.	PMID[9868162]
NPO4712	Lissoclinum patella	Species	Didemnidae	Eukaryota	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	7
Others	1

Activity Type	# Activity
Cell Line	7
NON-MOLECULAR	1

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT137	Cell Line	L1210	Mus musculus	IC50	=	0.35	ug.mL-1	PMID[479911]
NPT404	Cell Line	CCRF-CEM	Homo sapiens	IC50	=	0.01	ug.mL-1	PMID[479911]
NPT6463	Cell Line	MRC5CV1	Homo sapiens	IC50	=	0.22	ug.mL-1	PMID[479911]
NPT550	Cell Line	T-24	Homo sapiens	IC50	=	0.15	ug.mL-1	PMID[479911]
NPT6463	Cell Line	MRC5CV1	Homo sapiens	IC50	=	0.04	ug.mL-1	PMID[479911]
NPT550	Cell Line	T-24	Homo sapiens	IC50	=	0.1	ug.mL-1	PMID[479911]
NPT91	Cell Line	KB	Homo sapiens	IC50	=	0.035	ug.mL-1	PMID[479913]
NPT20529	NON-MOLECULAR	NON-PROTEIN TARGET	n.a.	LC50	=	3000.0	nM	PMID[479912]

☑ 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 NPC120917 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	185
0.1-0.2	24496
0.2-0.3	14145
0.3-0.4	3570
0.4-0.5	181
0.5-0.6	73
0.6-0.7	25
0.7-0.8	13
0.8-0.85	0
0.85-0.9	2
0.9-0.95	6
0.95-1	1

Similarity Score	Similarity Level	Natural Product ID
0.9603	High Similarity	NPC74917
0.9286	High Similarity	NPC89592
0.9274	High Similarity	NPC51692
0.9032	High Similarity	NPC135558
0.8968	High Similarity	NPC267605
0.872	High Similarity	NPC214375
0.775	Intermediate Similarity	NPC174652
0.7688	Intermediate Similarity	NPC475330
0.764	Intermediate Similarity	NPC263485
0.764	Intermediate Similarity	NPC229160
0.764	Intermediate Similarity	NPC25316
0.7622	Intermediate Similarity	NPC103268
0.7551	Intermediate Similarity	NPC475390
0.7532	Intermediate Similarity	NPC237219
0.7516	Intermediate Similarity	NPC475534
0.7516	Intermediate Similarity	NPC476080
0.7407	Intermediate Similarity	NPC161242
0.7208	Intermediate Similarity	NPC50274
0.7099	Intermediate Similarity	NPC164006
0.7099	Intermediate Similarity	NPC476103
0.7037	Intermediate Similarity	NPC24990
0.6954	Remote Similarity	NPC469801
0.6937	Remote Similarity	NPC522
0.6937	Remote Similarity	NPC56058
0.6886	Remote Similarity	NPC132662
0.6829	Remote Similarity	NPC34319
0.6748	Remote Similarity	NPC222391
0.6728	Remote Similarity	NPC201014
0.6728	Remote Similarity	NPC110129
0.6727	Remote Similarity	NPC256912
0.6606	Remote Similarity	NPC475554
0.6603	Remote Similarity	NPC319751
0.6543	Remote Similarity	NPC217981
0.6519	Remote Similarity	NPC473398
0.6509	Remote Similarity	NPC134480
0.6478	Remote Similarity	NPC119481
0.6471	Remote Similarity	NPC473704
0.6364	Remote Similarity	NPC216720
0.6325	Remote Similarity	NPC210424
0.6044	Remote Similarity	NPC329961
0.6	Remote Similarity	NPC96016
0.5978	Remote Similarity	NPC165538
0.5956	Remote Similarity	NPC122427
0.5954	Remote Similarity	NPC101980
0.5954	Remote Similarity	NPC470146
0.5954	Remote Similarity	NPC97078
0.5738	Remote Similarity	NPC49051
0.5731	Remote Similarity	NPC315252
0.568	Remote Similarity	NPC14101

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 NPC120917 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	106
0.1-0.2	1626
0.2-0.3	5057
0.3-0.4	2137
0.4-0.5	178
0.5-0.6	45
0.6-0.7	1
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
0.6929	Remote Similarity	NPD9579	Approved
0.581	Remote Similarity	NPD2957	Phase 2
0.5706	Remote Similarity	NPD6915	Approved
0.5658	Remote Similarity	NPD6121	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