NPASS Compound

Natural Product: NPC216673

Natural Product ID	NPC216673
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	CVNRGMCZFLKLMH-JRCSGKFVSA-N
IUPAC Name	n.a.
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	n.a.
PubChem CID	11431483
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000002] Organoheterocyclic compounds [CHEMONTID:0001634] Naphthofurans

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 69 0 0 0 0 0 0 0 0999 V2000 3.1656 2.9753 2.1916 C 0 0 0 0 0 0 0 0 0 0 0 0 2.9882 2.5811 0.7620 C 0 0 0 0 0 0 0 0 0 0 0 0 3.2183 3.3515 -0.1823 O 0 0 0 0 0 0 0 0 0 0 0 0 2.5502 1.3068 0.4855 O 0 0 0 0 0 0 0 0 0 0 0 0 2.3323 0.7777 -0.7867 C 0 0 1 0 0 0 0 0 0 0 0 0 3.3207 -0.3515 -1.0761 C 0 0 0 0 0 0 0 0 0 0 0 0 3.0578 -1.5613 -0.2737 C 0 0 0 0 0 0 0 0 0 0 0 0 1.6509 -2.0396 -0.2208 C 0 0 0 0 0 0 0 0 0 0 0 0 1.3289 -2.8647 -1.4611 C 0 0 0 0 0 0 0 0 0 0 0 0 1.5608 -2.9827 0.9613 C 0 0 0 0 0 0 0 0 0 0 0 0 0.6828 -0.8950 -0.0516 C 0 0 2 0 0 0 0 0 0 0 0 0 -0.7504 -1.3121 -0.1141 C 0 0 2 0 0 0 0 0 0 0 0 0 -1.5842 -0.1621 0.4745 C 0 0 1 0 0 0 0 0 0 0 0 0 -1.4719 0.9660 -0.5175 C 0 0 2 0 0 0 0 0 0 0 0 0 -0.0033 1.3891 -0.5618 C 0 0 2 0 0 0 0 0 0 0 0 0 0.0474 2.5561 -1.5181 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.6208 3.7101 -0.8716 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.7777 3.5021 -0.1568 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.2012 4.7268 0.3433 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.2551 5.6216 -0.1083 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.3456 4.9873 -0.8164 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.2687 2.1380 -0.0871 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.4257 1.9323 0.3593 O 0 0 0 0 0 0 0 0 0 0 0 0 0.9012 0.2529 -0.9607 C 0 0 1 0 0 0 0 0 0 0 0 0 0.7122 -0.0186 -2.4112 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.9245 -0.5409 0.5662 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.6876 -0.4976 1.7120 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.1571 -0.0886 2.7694 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.1023 -0.9387 1.6345 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.0719 -2.5020 0.5265 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.7427 -3.5542 -0.0491 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.1035 -3.4646 -1.2344 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.0274 -4.7654 0.7281 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8952 -0.4159 1.2657 O 0 0 0 0 0 0 0 0 0 0 0 0 3.2005 2.0739 2.8345 H 0 0 0 0 0 0 0 0 0 0 0 0 2.3277 3.6011 2.5511 H 0 0 0 0 0 0 0 0 0 0 0 0 4.1432 3.4873 2.3273 H 0 0 0 0 0 0 0 0 0 0 0 0 2.5741 1.5641 -1.5269 H 0 0 0 0 0 0 0 0 0 0 0 0 3.4301 -0.5432 -2.1553 H 0 0 0 0 0 0 0 0 0 0 0 0 4.3209 0.0634 -0.7511 H 0 0 0 0 0 0 0 0 0 0 0 0 3.4641 -1.4185 0.7639 H 0 0 0 0 0 0 0 0 0 0 0 0 3.6783 -2.3944 -0.6986 H 0 0 0 0 0 0 0 0 0 0 0 0 0.3927 -2.5591 -1.9437 H 0 0 0 0 0 0 0 0 0 0 0 0 1.2052 -3.9532 -1.2185 H 0 0 0 0 0 0 0 0 0 0 0 0 2.2138 -2.8356 -2.1468 H 0 0 0 0 0 0 0 0 0 0 0 0 1.0293 -3.9354 0.6872 H 0 0 0 0 0 0 0 0 0 0 0 0 2.5724 -3.3184 1.2698 H 0 0 0 0 0 0 0 0 0 0 0 0 1.1077 -2.5099 1.8524 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.1425 -1.3998 -1.1710 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.1541 0.1920 1.4267 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.7710 0.6780 -1.5394 H 0 0 0 0 0 0 0 0 0 0 0 0 0.2711 1.6996 0.4648 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.6096 2.2939 -2.4000 H 0 0 0 0 0 0 0 0 0 0 0 0 1.0420 2.8631 -1.8209 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.0798 4.8983 0.9464 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.2301 6.6865 0.0706 H 0 0 0 0 0 0 0 0 0 0 0 0 1.5215 -0.6546 -2.8623 H 0 0 0 0 0 0 0 0 0 0 0 0 0.8426 0.9725 -2.9417 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.2706 -0.3828 -2.7066 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.2880 -1.6733 0.8513 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.7125 -0.0049 1.4682 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.4348 -1.4016 2.6017 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.6906 -4.6554 1.7787 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.5191 -5.6694 0.3353 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.1126 -4.9787 0.7398 H 0 0 0 0 0 0 0 0 0 0 0 0 1.7871 -0.6047 1.5922 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 2 0 2 4 1 0 4 5 1 0 5 6 1 0 6 7 1 0 7 8 1 0 8 9 1 0 8 10 1 0 8 11 1 0 11 12 1 0 12 13 1 0 13 14 1 0 14 15 1 0 15 16 1 0 16 17 1 0 17 18 2 0 18 19 1 0 19 20 2 0 20 21 1 0 18 22 1 0 22 23 2 0 15 24 1 0 24 25 1 6 13 26 1 0 26 27 1 0 27 28 2 0 27 29 1 0 12 30 1 0 30 31 1 0 31 32 2 0 31 33 1 0 11 34 1 1 24 5 1 0 24 11 1 0 22 14 1 0 21 17 1 0 1 35 1 0 1 36 1 0 1 37 1 0 5 38 1 6 6 39 1 0 6 40 1 0 7 41 1 0 7 42 1 0 9 43 1 0 9 44 1 0 9 45 1 0 10 46 1 0 10 47 1 0 10 48 1 0 12 49 1 6 13 50 1 1 14 51 1 6 15 52 1 1 16 53 1 0 16 54 1 0 19 55 1 0 20 56 1 0 25 57 1 0 25 58 1 0 25 59 1 0 29 60 1 0 29 61 1 0 29 62 1 0 33 63 1 0 33 64 1 0 33 65 1 0 34 66 1 0 M END

Standard InCHIKey	CVNRGMCZFLKLMH-JRCSGKFVSA-N
Standard InCHI	InChI=1S/C25H32O9/c1-12(26)32-18-7-9-23(4,5)25(30)22(34-14(3)28)21(33-13(2)27)19-16(24(18,25)6)11-17-15(20(19)29)8-10-31-17/h8,10,16,18-19,21-22,30H,7,9,11H2,1-6H3/t16-,18-,19+,21+,22-,24-,25+/m0/s1
SMILES	CC(=O)O[C@H]1CCC(C)(C)[C@@]2([C@H]([C@@H]([C@@H]3[C@H](Cc4c(cco4)C3=O)[C@@]12C)OC(=O)C)OC(=O)C)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	476.2	Volume:	470.024 ? Van der Waals volume.
Dense:	1.013	LogP:	1.823 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	2.158 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-3.804 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	6.0	Rigid Bonds:	24.0
TPSA:	129.34 ? Topological Polar Surface Area.	H-Bond Acceptor:	9.0
H-Bond Donor:	1.0	Rings:	4.0
Heavy Atoms:	9.0

MedChem Properties

QED Drug-Likeness Score:	0.517	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	4.918	Fsp³:	0.68
MCE-18:	112.762 ? 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:	Accepted
Golden Triangle Rule:	Rejected	BMS Rule:	0
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.241	Fluc inhibitor:	0.008 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.006 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.001 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.063	Promiscuous compounds:	0.516

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.038	MDCK Permeability:	-4.456
Pgp-inhibitor:	0.893	Pgp-substrate:	0.83
PAMPA:	0.904 ? 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):	0.129
20% Bioavailability (F20%):	0.457	30% Bioavailability (F30%):	0.848
50% Bioavailability (F50%):	0.975

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.001	MRP1:	0.995
Plasma Protein Binding (PPB):	70.818%	Volume Distribution (VD):	-0.101
Fu:	26.818% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.999
OATP1B3 inhibitor:	0.976	BCRP inhibitor:	0.05
BSEP inhibitor:	0.951

ADMET: Metabolism

CYP1A2-inhibitor:	0.0	CYP1A2-substrate:	0.203
CYP2C19-inhibitor:	0.209	CYP2C19-substrate:	0.004
CYP2C9-inhibitor:	0.0	CYP2C9-substrate:	0.863
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.004
CYP3A4-inhibitor:	0.258	CYP3A4-substrate:	0.705
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	1.0
HLM stability:	0.987 ? 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):

5.201

Half-life (T1/2):

0.884

ADMET: Toxicity

hERG Blockers:	0.019	hERG Blockers (10um):	0.102
Human Hepatotoxicity (H-HT):	0.455	Drug-induced Liver Injury (DILI):	0.883
AMES Toxicity:	0.639	Rat Oral Acute Toxicity:	0.594
Maximum Recommended Daily Dose:	0.427	Skin Sensitization:	0.88
Carcinogencity:	0.8	Eye Corrosion:	0.012
Eye Irritation:	0.555	Respiratory Toxicity:	0.267
Drug-induced Neurotoxicity:	0.017	Ototoxicity:	0.32
Hematotoxicity:	0.335	Drug-induced Nephrotoxicity:	0.734
Genotoxicity:	0.992	RPMI-8226 Immunitoxicity:	0.069
A549 Cytotoxicity:	0.107	Hek293 Cytotoxicity:	0.081
BCF:	0.561 ? 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:	3.39 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.946 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.51 ? 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
NPO7886	Eria tomentosa	Species	Orchidaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO11853	Eucalyptus froggattii	Species	Myrtaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO13248	Pistacia mexicana	Species	Anacardiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO11853	Eucalyptus froggattii	Species	Myrtaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO7886	Eria tomentosa	Species	Orchidaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO13248	Pistacia mexicana	Species	Anacardiaceae	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

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

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 NPC216673 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	11743
0.1-0.2	36452
0.2-0.3	1595
0.3-0.4	50
0.4-0.5	7
0.5-0.6	4
0.6-0.7	4
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
0.7	Intermediate Similarity	NPC288602
0.7	Intermediate Similarity	NPC88841
0.6901	Remote Similarity	NPC88007
0.6806	Remote Similarity	NPC188649
0.6714	Remote Similarity	NPC140952
0.6575	Remote Similarity	NPC285567
0.5584	Remote Similarity	NPC194499
0.5513	Remote Similarity	NPC68848
0.5467	Remote Similarity	NPC81405
0.5128	Remote Similarity	NPC56358

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC216673 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	3430
0.1-0.2	5668
0.2-0.3	52
0.3-0.4	0
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