NPASS Compound

Natural Product: NPC20697

Natural Product ID	NPC20697
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	FROHWGGMFSFTTA-PEYQONPESA-N
IUPAC Name	n.a.
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	n.a.
PubChem CID	72734301
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000002] Organoheterocyclic compounds [CHEMONTID:0001640] Naphthopyrans

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 66 71 0 0 0 0 0 0 0 0999 V2000 5.7130 1.5218 -1.1040 C 0 0 0 0 0 0 0 0 0 0 0 0 5.7077 0.4890 0.0309 C 0 0 0 0 0 0 0 0 0 0 0 0 6.7119 -0.5504 -0.3090 C 0 0 0 0 0 0 0 0 0 0 0 0 4.3047 -0.0221 0.1547 C 0 0 2 0 0 0 0 0 0 0 0 0 3.8517 -0.8579 -0.9939 C 0 0 1 0 0 0 0 0 0 0 0 0 2.4663 -1.3214 -0.6950 C 0 0 0 0 0 0 0 0 0 0 0 0 1.7296 -0.7261 0.2350 C 0 0 0 0 0 0 0 0 0 0 0 0 0.3649 -1.1221 0.5846 C 0 0 2 0 0 0 0 0 0 0 0 0 -0.0260 -2.4782 0.1301 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.4428 -2.7854 0.6257 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.2996 -1.6881 0.1592 C 0 0 1 0 0 0 0 0 0 0 0 0 -3.7446 -1.7166 0.5871 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.1269 -0.3123 0.1758 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.1933 0.4463 -0.2550 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.5219 0.1810 -0.5102 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.3777 1.1693 -0.9444 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.8769 2.4451 -1.1218 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.5271 2.7055 -0.8603 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.6655 1.7303 -0.4279 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.3672 1.7438 -0.1212 N 0 0 0 0 0 0 0 0 0 0 0 0 -3.0134 0.4992 0.2530 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.9049 -0.3363 0.7171 C 0 0 1 0 0 0 0 0 0 0 0 0 -1.9200 -0.3365 2.2253 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.5596 -0.0061 0.1465 C 0 0 2 0 0 0 0 0 0 0 0 0 -0.7205 -0.0080 -1.3776 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.0186 1.3213 0.5274 C 0 0 0 0 0 0 0 0 0 0 0 0 1.2018 1.3537 1.3647 C 0 0 0 0 0 0 0 0 0 0 0 0 2.2934 0.4298 0.9986 C 0 0 2 0 0 0 0 0 0 0 0 0 3.3734 0.9999 0.3349 O 0 0 0 0 0 0 0 0 0 0 0 0 3.7606 -0.0874 -2.1659 O 0 0 0 0 0 0 0 0 0 0 0 0 6.0818 1.1867 1.1783 O 0 0 0 0 0 0 0 0 0 0 0 0 6.6198 2.1837 -0.9976 H 0 0 0 0 0 0 0 0 0 0 0 0 5.8102 1.0347 -2.0902 H 0 0 0 0 0 0 0 0 0 0 0 0 4.8263 2.1545 -1.0939 H 0 0 0 0 0 0 0 0 0 0 0 0 7.5110 -0.5673 0.4894 H 0 0 0 0 0 0 0 0 0 0 0 0 7.2706 -0.3300 -1.2505 H 0 0 0 0 0 0 0 0 0 0 0 0 6.3248 -1.5827 -0.3504 H 0 0 0 0 0 0 0 0 0 0 0 0 4.2854 -0.6828 1.0685 H 0 0 0 0 0 0 0 0 0 0 0 0 4.4587 -1.7696 -1.1573 H 0 0 0 0 0 0 0 0 0 0 0 0 2.0562 -2.1618 -1.2506 H 0 0 0 0 0 0 0 0 0 0 0 0 0.3059 -1.1227 1.7135 H 0 0 0 0 0 0 0 0 0 0 0 0 0.6260 -3.2051 0.6878 H 0 0 0 0 0 0 0 0 0 0 0 0 0.1079 -2.6928 -0.9254 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.4493 -3.0146 1.6887 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.7856 -3.7280 0.1075 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.2822 -1.6406 -0.9376 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.2785 -2.4670 -0.0198 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.8917 -1.8755 1.6636 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.9224 -0.8110 -0.3749 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.4251 1.0174 -1.1589 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.5390 3.2319 -1.4628 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.1335 3.7074 -0.9996 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.7155 2.5637 -0.1571 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.9973 -0.2642 2.5322 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.5277 -1.2409 2.6844 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.4523 0.5962 2.5703 H 0 0 0 0 0 0 0 0 0 0 0 0 0.0183 0.6870 -1.8522 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.7216 0.4079 -1.5810 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.5624 -0.9877 -1.8190 H 0 0 0 0 0 0 0 0 0 0 0 0 0.1576 1.9979 -0.3562 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.8195 1.8648 1.1119 H 0 0 0 0 0 0 0 0 0 0 0 0 1.6112 2.4043 1.3155 H 0 0 0 0 0 0 0 0 0 0 0 0 0.9284 1.2339 2.4547 H 0 0 0 0 0 0 0 0 0 0 0 0 2.7242 -0.0249 1.9378 H 0 0 0 0 0 0 0 0 0 0 0 0 3.1451 0.6636 -1.9521 H 0 0 0 0 0 0 0 0 0 0 0 0 6.4619 0.5529 1.8451 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 1 0 2 4 1 0 4 5 1 0 5 6 1 0 6 7 2 0 7 8 1 0 8 9 1 0 9 10 1 0 10 11 1 0 11 12 1 0 12 13 1 0 13 14 1 0 14 15 2 0 15 16 1 0 16 17 2 0 17 18 1 0 18 19 2 0 19 20 1 0 20 21 1 0 21 22 1 0 22 23 1 1 22 24 1 0 24 25 1 6 24 26 1 0 26 27 1 0 27 28 1 0 28 29 1 0 5 30 1 0 2 31 1 0 29 4 1 0 28 7 1 0 24 8 1 0 22 11 1 0 21 13 2 0 19 14 1 0 1 32 1 0 1 33 1 0 1 34 1 0 3 35 1 0 3 36 1 0 3 37 1 0 4 38 1 1 5 39 1 6 6 40 1 0 8 41 1 1 9 42 1 0 9 43 1 0 10 44 1 0 10 45 1 0 11 46 1 6 12 47 1 0 12 48 1 0 15 49 1 0 16 50 1 0 17 51 1 0 18 52 1 0 20 53 1 0 23 54 1 0 23 55 1 0 23 56 1 0 25 57 1 0 25 58 1 0 25 59 1 0 26 60 1 0 26 61 1 0 27 62 1 0 27 63 1 0 28 64 1 1 30 65 1 0 31 66 1 0 M END

Standard InCHIKey	FROHWGGMFSFTTA-PEYQONPESA-N
Standard InCHI	InChI=1S/C27H35NO3/c1-25(2,30)24-21(29)14-18-19-10-9-15-13-17-16-7-5-6-8-20(16)28-23(17)27(15,4)26(19,3)12-11-22(18)31-24/h5-8,14-15,19,21-22,24,28-30H,9-13H2,1-4H3/t15-,19-,21+,22-,24-,26-,27+/m0/s1
SMILES	CC(C)([C@@H]1[C@@H](C=C2[C@@H]3CC[C@H]4Cc5c6ccccc6[nH]c5[C@]4(C)[C@@]3(C)CC[C@@H]2O1)O)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	421.26	Volume:	448.394 ? Van der Waals volume.
Dense:	0.939	LogP:	3.292 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	3.246 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-4.525 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	1.0	Rigid Bonds:	29.0
TPSA:	65.48 ? Topological Polar Surface Area.	H-Bond Acceptor:	4.0
H-Bond Donor:	3.0	Rings:	6.0
Heavy Atoms:	4.0

MedChem Properties

QED Drug-Likeness Score:	0.588	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	4.83	Fsp³:	0.63
MCE-18:	131.182 ? MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.	Lipinski Rule-of-5:	Rejected
Pfizer Rule:	Accepted	GSK Rule:	Accepted
Golden Triangle Rule:	Rejected	BMS Rule:	0
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.677	Fluc inhibitor:	0.001 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.663 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.005 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.01	Promiscuous compounds:	0.368

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.239	MDCK Permeability:	-4.875
Pgp-inhibitor:	0.046	Pgp-substrate:	0.353
PAMPA:	0.646 ? 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%):	0.054	30% Bioavailability (F30%):	0.303
50% Bioavailability (F50%):	0.963

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.742	MRP1:	0.197
Plasma Protein Binding (PPB):	93.83%	Volume Distribution (VD):	-0.069
Fu:	5.066% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	1.0
OATP1B3 inhibitor:	0.997	BCRP inhibitor:	0.971
BSEP inhibitor:	1.0

ADMET: Metabolism

CYP1A2-inhibitor:	0.244	CYP1A2-substrate:	0.002
CYP2C19-inhibitor:	0.211	CYP2C19-substrate:	0.015
CYP2C9-inhibitor:	0.003	CYP2C9-substrate:	0.827
CYP2D6-inhibitor:	0.089	CYP2D6-substrate:	0.001
CYP3A4-inhibitor:	1.0	CYP3A4-substrate:	1.0
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.941
HLM stability:	0.007 ? 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):

12.203

Half-life (T1/2):

1.329

ADMET: Toxicity

hERG Blockers:	0.416	hERG Blockers (10um):	0.517
Human Hepatotoxicity (H-HT):	0.751	Drug-induced Liver Injury (DILI):	0.474
AMES Toxicity:	0.708	Rat Oral Acute Toxicity:	0.857
Maximum Recommended Daily Dose:	0.957	Skin Sensitization:	0.83
Carcinogencity:	0.553	Eye Corrosion:	0.0
Eye Irritation:	0.111	Respiratory Toxicity:	0.93
Drug-induced Neurotoxicity:	0.274	Ototoxicity:	0.783
Hematotoxicity:	0.328	Drug-induced Nephrotoxicity:	0.591
Genotoxicity:	0.959	RPMI-8226 Immunitoxicity:	0.135
A549 Cytotoxicity:	0.252	Hek293 Cytotoxicity:	0.564
BCF:	2.393 ? 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:	4.617 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	6.025 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	5.567 ? 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
NPO40587	Penicillium sp. (strain ZO-R1-1)	Strain	Aspergillaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[31117519]
NPO40587	Penicillium sp. (strain ZO-R1-1)	Strain	Aspergillaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]

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 Type	# Activity
Cell line	1

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
NPT179	Cell line	A2780	Homo sapiens	IC50	=	28500.0	nM	PMID[31117519]

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 NPC20697 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	11136
0.1-0.2	37354
0.2-0.3	1168
0.3-0.4	147
0.4-0.5	21
0.5-0.6	20
0.6-0.7	10
0.7-0.8	0
0.8-0.85	1
0.85-0.9	0
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Natural Product ID
0.8158	Intermediate Similarity	NPC34271
0.7722	Intermediate Similarity	NPC123019
0.6848	Remote Similarity	NPC609845
0.6463	Remote Similarity	NPC231342
0.6456	Remote Similarity	NPC165201
0.619	Remote Similarity	NPC119700
0.6186	Remote Similarity	NPC607140
0.6163	Remote Similarity	NPC224641
0.6145	Remote Similarity	NPC487208
0.6092	Remote Similarity	NPC487204
0.6071	Remote Similarity	NPC487209
0.6067	Remote Similarity	NPC602114
0.5882	Remote Similarity	NPC609321
0.5833	Remote Similarity	NPC6093
0.5824	Remote Similarity	NPC611491
0.573	Remote Similarity	NPC235900
0.5667	Remote Similarity	NPC18661
0.5652	Remote Similarity	NPC600666
0.5543	Remote Similarity	NPC471284
0.5385	Remote Similarity	NPC484479
0.5368	Remote Similarity	NPC36356
0.5349	Remote Similarity	NPC97525
0.5349	Remote Similarity	NPC198339
0.5294	Remote Similarity	NPC602195
0.5238	Remote Similarity	NPC99428
0.5222	Remote Similarity	NPC489082
0.5217	Remote Similarity	NPC487201
0.5217	Remote Similarity	NPC487207
0.5181	Remote Similarity	NPC302191
0.5161	Remote Similarity	NPC489199
0.5053	Remote Similarity	NPC486860
0.5051	Remote Similarity	NPC609846

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC20697 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	4544
0.1-0.2	4483
0.2-0.3	122
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