NPASS Compound

Structure

NPC74917 OpenBabel07101718182D 51 55 0 0 1 0 0 0 0 0999 V2000 -0.7040 -4.6160 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.8032 4.2032 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.8603 -2.3235 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.9686 -4.1622 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8642 2.8334 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.9514 3.8242 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.3148 -2.3073 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.6732 4.1516 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.7675 4.5944 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.4881 -4.0730 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.2931 3.2679 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.1367 -3.4812 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.2063 -0.6305 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.2445 0.4357 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.8649 -2.3808 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.3296 2.8047 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.4099 -3.1224 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -6.2280 3.2421 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -3.2791 3.6576 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 -4.4560 -2.9137 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.8555 -0.7670 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.6877 0.7571 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.3175 -1.5474 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 -0.9016 1.7565 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 -2.1940 -2.5794 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -5.3186 2.6872 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -2.9514 3.1199 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -5.4075 -2.4693 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.2672 -1.6498 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.2110 1.7780 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.8205 2.5918 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.1538 -2.9282 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.2103 3.0899 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.6877 -0.5285 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.4428 0.4939 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.7914 -2.2024 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 -5.8989 0.0995 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 -1.4895 -0.0948 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 -5.3223 -1.4875 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 -2.0661 1.4922 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 -2.2044 -1.6257 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 -5.1840 1.6304 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 -3.5970 2.2071 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 -6.2526 -2.9303 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.7605 -2.4683 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -6.6688 2.6249 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.9737 3.0496 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.4856 -3.4884 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.9085 3.6426 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -7.2445 -0.2071 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 10 1 0 0 0 0 2 11 1 0 0 0 0 3 15 1 0 0 0 0 4 15 1 0 0 0 0 5 16 1 0 0 0 0 6 16 1 0 0 0 0 10 17 1 0 0 0 0 11 18 1 0 0 0 0 12 48 1 0 0 0 0 13 21 2 0 0 0 0 13 51 1 0 0 0 0 14 22 2 0 0 0 0 14 50 1 0 0 0 0 17 7 1 1 0 0 0 18 8 1 6 0 0 0 19 9 1 6 0 0 0 19 27 1 0 0 0 0 19 49 1 0 0 0 0 20 12 1 1 0 0 0 20 28 1 0 0 0 0 20 36 1 0 0 0 0 21 29 1 0 0 0 0 21 38 1 0 0 0 0 22 30 1 0 0 0 0 22 37 1 0 0 0 0 23 15 1 6 0 0 0 23 34 1 0 0 0 0 23 39 1 0 0 0 0 24 16 1 6 0 0 0 24 35 1 0 0 0 0 24 40 1 0 0 0 0 25 17 1 1 0 0 0 25 32 1 0 0 0 0 25 41 1 0 0 0 0 26 18 1 1 0 0 0 26 33 1 0 0 0 0 26 42 1 0 0 0 0 27 31 1 1 0 0 0 27 43 1 0 0 0 0 28 39 2 3 0 0 0 28 44 1 0 0 0 0 29 41 2 3 0 0 0 29 45 1 0 0 0 0 30 42 2 3 0 0 0 30 46 1 0 0 0 0 31 40 2 3 0 0 0 31 47 1 0 0 0 0 32 36 2 0 0 0 0 32 48 1 0 0 0 0 33 43 2 0 0 0 0 33 49 1 0 0 0 0 34 37 2 0 0 0 0 34 50 1 0 0 0 0 35 38 2 0 0 0 0 35 51 1 0 0 0 0 M END $$$$

Physi-Chem Properties

Molecular Weight:	742.33
Volume:	722.503
LogP:	4.517
LogD:	3.915
LogS:	-2.252
# Rotatable Bonds:	6
TPSA:	203.43
# H-Bond Aceptor:	14
# H-Bond Donor:	5
# Rings:	5
# Heavy Atoms:	16

MedChem Properties

QED Drug-Likeness Score:	0.173
Synthetic Accessibility Score:	7.873
Fsp3:	0.629
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:	-4.665
MDCK Permeability:	1.8844355508917943e-05
Pgp-inhibitor:	0.963
Pgp-substrate:	0.999
Human Intestinal Absorption (HIA):	0.021
20% Bioavailability (F20%):	0.826
30% Bioavailability (F30%):	0.977

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.838
Plasma Protein Binding (PPB):	60.64137649536133%
Volume Distribution (VD):	2.946
Pgp-substrate:	22.296138763427734%

ADMET: Metabolism

CYP1A2-inhibitor:	0.047
CYP1A2-substrate:	0.051
CYP2C19-inhibitor:	0.049
CYP2C19-substrate:	0.07
CYP2C9-inhibitor:	0.076
CYP2C9-substrate:	0.017
CYP2D6-inhibitor:	0.002
CYP2D6-substrate:	0.02
CYP3A4-inhibitor:	0.044
CYP3A4-substrate:	0.915

ADMET: Excretion

Clearance (CL):	1.473
Half-life (T1/2):	0.06

ADMET: Toxicity

hERG Blockers:	0.004
Human Hepatotoxicity (H-HT):	1.0
Drug-inuced Liver Injury (DILI):	0.993
AMES Toxicity:	0.003
Rat Oral Acute Toxicity:	0.093
Maximum Recommended Daily Dose:	0.926
Skin Sensitization:	0.013
Carcinogencity:	0.019
Eye Corrosion:	0.003
Eye Irritation:	0.006
Respiratory Toxicity:	0.439

Download Data

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

Natural Product: NPC74917

Natural Product ID:	NPC74917
*Common Name:**	Patellamide A
IUPAC Name:	n.a.
Synonyms:
Standard InCHIKey:	ZGJIVWQOEHQWLW-SWTUTNCKSA-N
Standard InCHI:	InChI=1S/C35H50N8O6S2/c1-10-17(7)25-32-36-20(12-48-32)28(44)39-23(15(3)4)34-37-22(14-50-34)30(46)42-26(18(8)11-2)33-43-27(19(9)49-33)31(47)40-24(16(5)6)35-38-21(13-51-35)29(45)41-25/h13-20,23-27H,10-12H2,1-9H3,(H,39,44)(H,40,47)(H,41,45)(H,42,46)/t17-,18-,19+,20-,23+,24+,25-,26-,27-/m0/s1
SMILES:	CC[C@@H]([C@@H]1N=C(O)c2csc(n2)[C@H](N=C(O)[C@H]2N=C(O[C@@H]2C)[C@@H](N=C(c2nc([C@H](N=C([C@H]3N=C1OC3)O)C(C)C)sc2)O)[C@H](CC)C)C(C)C)C
Synthetic Gene Cluster:	BGC0000475;
ChEMBL Identifier:	CHEMBL448385
PubChem CID:	157454
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	3
Others	3

Activity Type	# Activity
Cell Line	4
NON-MOLECULAR	2

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT137	Cell Line	L1210	Mus musculus	IC50	=	2.0	ug.mL-1	PMID[523494]
NPT91	Cell Line	KB	Homo sapiens	IC50	=	3.0	ug.mL-1	PMID[523496]
NPT137	Cell Line	L1210	Mus musculus	Activity	=	150.0	Zone units	PMID[523496]
NPT730	Cell Line	MC-38	Mus musculus	Activity	=	160.0	Zone units	PMID[523496]
NPT20529	NON-MOLECULAR	NON-PROTEIN TARGET	n.a.	IC50	=	90.0	nM	PMID[523495]
NPT20529	NON-MOLECULAR	NON-PROTEIN TARGET	n.a.	Activity	=	0.0	Zone units	PMID[523496]

☑ 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 NPC74917 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	180
0.1-0.2	20829
0.2-0.3	17642
0.3-0.4	3735
0.4-0.5	188
0.5-0.6	75
0.6-0.7	25
0.7-0.8	14
0.8-0.85	0
0.85-0.9	1
0.9-0.95	6
0.95-1	2

Similarity Score	Similarity Level	Natural Product ID
0.9603	High Similarity	NPC120917
0.9516	High Similarity	NPC89592
0.935	High Similarity	NPC267605
0.935	High Similarity	NPC51692
0.9106	High Similarity	NPC135558
0.879	High Similarity	NPC214375
0.7688	Intermediate Similarity	NPC229160
0.7688	Intermediate Similarity	NPC25316
0.7688	Intermediate Similarity	NPC263485
0.7625	Intermediate Similarity	NPC475330
0.7603	Intermediate Similarity	NPC475390
0.7582	Intermediate Similarity	NPC237219
0.7578	Intermediate Similarity	NPC174652
0.7552	Intermediate Similarity	NPC103268
0.7453	Intermediate Similarity	NPC161242
0.7346	Intermediate Similarity	NPC476080
0.7346	Intermediate Similarity	NPC475534
0.7255	Intermediate Similarity	NPC50274
0.7143	Intermediate Similarity	NPC164006
0.7081	Intermediate Similarity	NPC24990
0.7	Intermediate Similarity	NPC469801
0.6981	Remote Similarity	NPC56058
0.6981	Remote Similarity	NPC522
0.6933	Remote Similarity	NPC476103
0.6928	Remote Similarity	NPC132662
0.6871	Remote Similarity	NPC34319
0.679	Remote Similarity	NPC222391
0.677	Remote Similarity	NPC110129
0.677	Remote Similarity	NPC201014
0.6768	Remote Similarity	NPC256912
0.6646	Remote Similarity	NPC475554
0.6645	Remote Similarity	NPC319751
0.6584	Remote Similarity	NPC217981
0.6561	Remote Similarity	NPC473398
0.6548	Remote Similarity	NPC134480
0.6519	Remote Similarity	NPC119481
0.6509	Remote Similarity	NPC473704
0.6402	Remote Similarity	NPC216720
0.6364	Remote Similarity	NPC210424
0.6077	Remote Similarity	NPC329961
0.6034	Remote Similarity	NPC96016
0.6011	Remote Similarity	NPC165538
0.5989	Remote Similarity	NPC122427
0.5988	Remote Similarity	NPC101980
0.5988	Remote Similarity	NPC97078
0.5988	Remote Similarity	NPC470146
0.5858	Remote Similarity	NPC315252
0.5714	Remote Similarity	NPC14101
0.5683	Remote Similarity	NPC49051
0.5621	Remote Similarity	NPC475568

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 NPC74917 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	110
0.1-0.2	1516
0.2-0.3	5155
0.3-0.4	2161
0.4-0.5	164
0.5-0.6	43
0.6-0.7	0
0.7-0.8	1
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
0.6978	Remote Similarity	NPD9579	Approved
0.5843	Remote Similarity	NPD2957	Phase 2
0.574	Remote Similarity	NPD6915	Approved
0.5695	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