NPASS Compound

Natural Product: NPC489061

Natural Product ID	NPC489061
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	IZUFMCOHAOFHPW-NUATZEMDSA-N
IUPAC Name	n.a.
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	n.a.
PubChem CID	n.a.
Chemical Classification	CHEMONTID:0000000 [Organic compounds]

The Chemical Classification was calculated by Classyfire, a software for chemical taxonomy calculation. Reference: DOI:10.1186/s13321-016-0174-y.

Chemical Representations

RDKit 3D 54 56 0 0 0 0 0 0 0 0999 V2000 -3.2945 -2.0454 1.2569 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.5724 -1.3202 0.2038 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.3318 -1.8446 -0.9956 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.6135 -1.1619 -2.0860 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.5901 -0.1534 -1.6316 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.6385 0.0543 -0.1136 C 0 0 2 0 0 0 0 0 0 0 0 0 -2.0344 0.0899 0.3845 C 0 0 1 0 0 0 0 0 0 0 0 0 -2.9775 0.9812 -0.3286 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.9791 0.3003 1.8713 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.4839 1.6794 2.0846 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.3307 2.1260 1.2926 C 0 0 2 0 0 0 0 0 0 0 0 0 -0.6634 3.4513 0.6370 C 0 0 0 0 0 0 0 0 0 0 0 0 0.2988 1.1280 0.3285 C 0 0 2 0 0 0 0 0 0 0 0 0 0.8145 1.9517 -0.8214 C 0 0 0 0 0 0 0 0 0 0 0 0 1.4603 0.5599 1.0946 C 0 0 0 0 0 0 0 0 0 0 0 0 2.3531 -0.4088 0.5532 C 0 0 0 0 0 0 0 0 0 0 0 0 2.2839 -1.6568 1.0639 C 0 0 0 0 0 0 0 0 0 0 0 0 3.1259 -2.7495 0.6215 C 0 0 0 0 0 0 0 0 0 0 0 0 3.0337 -3.9031 1.1144 O 0 0 0 0 0 0 0 0 0 0 0 0 4.1120 -2.5300 -0.4199 C 0 0 0 0 0 0 0 0 0 0 0 0 4.2043 -1.3190 -0.9313 C 0 0 0 0 0 0 0 0 0 0 0 0 3.3375 -0.2047 -0.4743 C 0 0 0 0 0 0 0 0 0 0 0 0 3.5392 0.9033 -1.0456 O 0 0 0 0 0 0 0 0 0 0 0 0 5.1620 -1.0840 -1.9466 N 0 0 0 0 0 0 0 0 0 0 0 0 1.3657 -1.9749 2.0865 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.2756 -1.5517 1.5195 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.6716 -2.0221 2.1892 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.4295 -3.0790 0.9486 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.7092 -2.8621 -1.1552 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.3499 -0.6839 -2.7989 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.1391 -1.9662 -2.7063 H 0 0 0 0 0 0 0 0 0 0 0 0 0.4045 -0.5288 -1.9403 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.7686 0.7775 -2.1944 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.2340 -0.9127 0.2642 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.4477 1.6661 0.4043 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.5621 1.5831 -1.1328 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.8619 0.4407 -0.7818 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.3279 -0.4919 2.2908 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.0177 0.2330 2.2561 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.3131 1.7666 3.2078 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.3699 2.3723 1.9477 H 0 0 0 0 0 0 0 0 0 0 0 0 0.4571 2.4511 2.0518 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.4764 3.4252 -0.0807 H 0 0 0 0 0 0 0 0 0 0 0 0 0.2639 3.9815 0.2846 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.0308 4.1548 1.4506 H 0 0 0 0 0 0 0 0 0 0 0 0 0.0057 2.6503 -1.2038 H 0 0 0 0 0 0 0 0 0 0 0 0 1.6203 2.6170 -0.5405 H 0 0 0 0 0 0 0 0 0 0 0 0 1.1052 1.3654 -1.7122 H 0 0 0 0 0 0 0 0 0 0 0 0 2.1007 1.4443 1.4853 H 0 0 0 0 0 0 0 0 0 0 0 0 0.9922 0.2278 2.0848 H 0 0 0 0 0 0 0 0 0 0 0 0 4.7568 -3.3520 -0.7651 H 0 0 0 0 0 0 0 0 0 0 0 0 5.7805 -0.2381 -1.8849 H 0 0 0 0 0 0 0 0 0 0 0 0 5.2912 -1.7076 -2.7609 H 0 0 0 0 0 0 0 0 0 0 0 0 0.6258 -2.6295 1.8911 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 2 0 3 4 1 0 4 5 1 0 5 6 1 0 6 7 1 0 7 8 1 6 7 9 1 0 9 10 1 0 10 11 1 0 11 12 1 0 11 13 1 0 13 14 1 6 13 15 1 0 15 16 1 0 16 17 2 0 17 18 1 0 18 19 2 0 18 20 1 0 20 21 2 0 21 22 1 0 22 23 2 0 21 24 1 0 17 25 1 0 7 2 1 0 22 16 1 0 13 6 1 0 1 26 1 0 1 27 1 0 1 28 1 0 3 29 1 0 4 30 1 0 4 31 1 0 5 32 1 0 5 33 1 0 6 34 1 1 8 35 1 0 8 36 1 0 8 37 1 0 9 38 1 0 9 39 1 0 10 40 1 0 10 41 1 0 11 42 1 1 12 43 1 0 12 44 1 0 12 45 1 0 14 46 1 0 14 47 1 0 14 48 1 0 15 49 1 0 15 50 1 0 20 51 1 0 24 52 1 0 24 53 1 0 25 54 1 0 M END

Standard InCHIKey	IZUFMCOHAOFHPW-NUATZEMDSA-N
Standard InCHI	InChI=1S/C21H29NO3/c1-12-6-5-7-17-20(12,3)9-8-13(2)21(17,4)11-14-18(24)15(22)10-16(23)19(14)25/h6,10,13,17,25H,5,7-9,11,22H2,1-4H3/t13-,17+,20+,21+/m0/s1
SMILES	CC1=CCC[C@@H]2[C@]1(C)CC[C@H](C)[C@@]2(C)CC1=C(C(=O)C=C(C1=O)N)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	343.21	Volume:	370.288 ? Van der Waals volume.
Dense:	0.927	LogP:	2.875 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	2.921 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-4.358 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	2.0	Rigid Bonds:	19.0
TPSA:	80.39 ? Topological Polar Surface Area.	H-Bond Acceptor:	4.0
H-Bond Donor:	3.0	Rings:	3.0
Heavy Atoms:	4.0

MedChem Properties

QED Drug-Likeness Score:	0.587	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	4.469	Fsp³:	0.619
MCE-18:	56.824 ? MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.	Lipinski Rule-of-5:	Rejected
Pfizer Rule:	Rejected	GSK Rule:	Rejected
Golden Triangle Rule:	Rejected	BMS Rule:	0
Chelating Alert:	0	PAINS Alert:	1
Colloidal aggregators:	0.721	Fluc inhibitor:	0.456 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.32 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.06 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.304	Promiscuous compounds:	0.174

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.002	MDCK Permeability:	-4.769
Pgp-inhibitor:	0.075	Pgp-substrate:	0.006
PAMPA:	0.479 ? The experimental data for Peff was logarithmically transformed (logPeff). Molecules with log Peff values below 2.0 were classified as low-permeability (Category 0), while those with log Peff values exceeding 2.5 were classified as high-permeability (Category 1).	Human Intestinal Absorption (HIA):	0.0
20% Bioavailability (F20%):	0.016	30% Bioavailability (F30%):	0.053
50% Bioavailability (F50%):	0.428

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.229	MRP1:	0.813
Plasma Protein Binding (PPB):	84.964%	Volume Distribution (VD):	0.188
Fu:	11.233% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.998
OATP1B3 inhibitor:	0.998	BCRP inhibitor:	0.027
BSEP inhibitor:	0.785

ADMET: Metabolism

CYP1A2-inhibitor:	0.195	CYP1A2-substrate:	0.309
CYP2C19-inhibitor:	0.086	CYP2C19-substrate:	0.004
CYP2C9-inhibitor:	0.175	CYP2C9-substrate:	0.004
CYP2D6-inhibitor:	0.005	CYP2D6-substrate:	0.003
CYP3A4-inhibitor:	0.021	CYP3A4-substrate:	0.165
CYP2B6-substrate:	0.001	CYP2C8-inhibitor:	0.085
HLM stability:	0.866 ? Human liver microsomal (HLM) stability. Category 0: stable+ (HLM > 30 min); Category 1: unstable- (HLM ≤ 30 min). The output value is the probability of human liver microsomal instability, where a value closer to 1 indicates a higher likelihood of instability.

ADMET: Excretion

Clearance (CL):

5.469

Half-life (T1/2):

0.867

ADMET: Toxicity

hERG Blockers:	0.031	hERG Blockers (10um):	0.158
Human Hepatotoxicity (H-HT):	0.703	Drug-induced Liver Injury (DILI):	0.517
AMES Toxicity:	0.562	Rat Oral Acute Toxicity:	0.347
Maximum Recommended Daily Dose:	0.587	Skin Sensitization:	0.924
Carcinogencity:	0.94	Eye Corrosion:	0.008
Eye Irritation:	0.872	Respiratory Toxicity:	0.663
Drug-induced Neurotoxicity:	0.467	Ototoxicity:	0.255
Hematotoxicity:	0.628	Drug-induced Nephrotoxicity:	0.484
Genotoxicity:	0.921	RPMI-8226 Immunitoxicity:	0.088
A549 Cytotoxicity:	0.146	Hek293 Cytotoxicity:	0.318
BCF:	2.174 ? Bioconcentration factors are used for considering secondary poisoning potential and assessing risks to human health via the food chain. The unit is -log10[(mg/L)/(1000*MW)].	IGC50:	4.867 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	6.045 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	5.725 ? 96 hour fathead minnow LC50. The unit of LC50FM is -log10[(mg/L)/(1000*MW)].

Species Source

Organism ID	Organism Name	Taxonomy Level	Family	SuperKingdom	Isolation Part	Collection Location	Collection Time	Reference
NPO13603	Dactylospongia metachromia	Species	Thorectidae	Eukaryota	n.a.	n.a.	n.a.	PMID[24479418]
NPO13603	Dactylospongia metachromia	Species	Thorectidae	Eukaryota	n.a.	n.a.	n.a.	PMID[33387695]
NPO13603	Dactylospongia metachromia	Species	Thorectidae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO13603	Dactylospongia metachromia	Species	Thorectidae	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	Organism Name	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	1
Activity	3

Activity Type	# Activity
Cell line	4

Molecular-level activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference

In vitro activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT165	Cell line	HeLa	Homo sapiens	IC50	=	18000.0	nM	PMID[33387695]
NPT165	Cell line	HeLa	Homo sapiens	Activity	=	27.2	%	PMID[33387695]
NPT165	Cell line	HeLa	Homo sapiens	Activity	=	46.5	%	PMID[33387695]
NPT165	Cell line	HeLa	Homo sapiens	Activity	=	26.3	%	PMID[33387695]

In vivo activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference

Experimental ADME

Experiment Model	Experiment Tissue	ADME Type	ADME Relation	ADME Value	ADME Unit	Reference

Experimental Toxicity

Quantitative toxicity

Experiment Model	Experiment Organism	Toxicity Type	Toxicity Relation	Toxicity Value	Toxicity Unit	Reference

Common Abbreviations:
LC: Lethal Concentration; LD: Lethal Dose; LT:Lethal Time; NOAEL: No-observed-adverse-effect Level; BMDL: Benchmark Dose Lower Confidence Limit; BMD: Benchmark Dose; BMC:Benchmark Concentration; LOAEL: Lowest Observed Adverse Effect Level; RfD:Reference Dose; RfC:Reference Concentration; MRL: Minimal Risk Level; MEG: Maximum Exposure Guideline; PAC: Protective Action Criteria

Categorical toxicity labels

Hepatotoxicity	Carcinogenicity	Mutagenicity	Cardiotoxicity	Respiratory Toxicity	Eye Irritation	Endocrine Disruption

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 toxicity records from domain-specific databases. These databases include:
☉ ToxValDB: a curated database that compiles quantitative toxicity values for chemicals from diverse public sources to support toxicological research and risk assessment.
☉ TOXRIC: a comprehensive, free-to-access, online database providing toxicological/feature data. The toxicity labels are retrieved from this database. [PMID: 36400569]

Chemically structural similarity

Similar Active Natural Products in NPASS

Top-200 similar NPs were calculated against the active-NP-set (includes approximately 50,000 NPs with experimentally-derived bioactivity available in NPASS)

Similarity is measured using the Tanimoto coefficient (Tc) , which compares the binary fingerprints of two molecules. Tc is calculated as the intersection divided by the union of '1' bits in the fingerprints, ranging from 0 to 1, with 1 indicating highest similarity.

● The left chart: Distribution of similarity level between NPC489061 and all remaining natural products in the NPASS database.
● The right table: Most similar natural products (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	18897
0.1-0.2	28910
0.2-0.3	1923
0.3-0.4	63
0.4-0.5	28
0.5-0.6	17
0.6-0.7	11
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	Natural Product ID
0.7544	Intermediate Similarity	NPC604451
0.7288	Intermediate Similarity	NPC34193
0.7288	Intermediate Similarity	NPC218631
0.7288	Intermediate Similarity	NPC606042
0.7193	Intermediate Similarity	NPC260139
0.7193	Intermediate Similarity	NPC10001
0.7167	Intermediate Similarity	NPC489062
0.7037	Intermediate Similarity	NPC55869
0.6719	Remote Similarity	NPC72688
0.6719	Remote Similarity	NPC611550
0.6429	Remote Similarity	NPC302761
0.6333	Remote Similarity	NPC263997
0.6333	Remote Similarity	NPC8518
0.6271	Remote Similarity	NPC603061
0.6232	Remote Similarity	NPC49417
0.6232	Remote Similarity	NPC119326
0.6143	Remote Similarity	NPC603298
0.6129	Remote Similarity	NPC489707
0.6111	Remote Similarity	NPC2672
0.5902	Remote Similarity	NPC99308
0.5733	Remote Similarity	NPC603297
0.5714	Remote Similarity	NPC481276
0.5714	Remote Similarity	NPC481275
0.5714	Remote Similarity	NPC601986
0.55	Remote Similarity	NPC108955
0.5455	Remote Similarity	NPC36626
0.5455	Remote Similarity	NPC602082
0.5366	Remote Similarity	NPC47190
0.5323	Remote Similarity	NPC602754
0.5294	Remote Similarity	NPC602428
0.5238	Remote Similarity	NPC601854
0.5094	Remote Similarity	NPC606666
0.5082	Remote Similarity	NPC473251
0.5082	Remote Similarity	NPC42586
0.507	Remote Similarity	NPC185929
0.5068	Remote Similarity	NPC606951

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC489061 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	6559
0.1-0.2	2558
0.2-0.3	32
0.3-0.4	1
0.4-0.5	0
0.5-0.6	0
0.6-0.7	0
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
		NPD

Bioactivity similarity

Similar Natural Products in NPASS

Similarity level is defined by 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