NPASS Compound

Natural Product: NPC476338

Natural Product ID	NPC476338
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	Kadsurenin C
IUPAC Name	(1S,5S,6R,7R,8S)-7-(3,4-dimethoxyphenyl)-8-hydroxy-5-methoxy-6-methyl-3-prop-2-enylbicyclo[3.2.1]oct-3-en-2-one
Synonyms	Kadsurenin C
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL571615
PubChem CID	45487142
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0002448] Benzenoids [CHEMONTID:0002279] Benzene and substituted derivatives [CHEMONTID:0004113] Methoxybenzenes [CHEMONTID:0004111] Dimethoxybenzenes

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

Chemical Representations

RDKit 2D 52 54 0 0 0 0 0 0 0 0999 V2000 6.3943 1.3846 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 5.6443 0.0855 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 4.1443 0.0855 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.6443 0.0855 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.8943 1.3846 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.3943 1.2135 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8578 2.6401 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.1459 3.7548 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.2760 0.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.3943 -1.2135 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.8943 -1.2135 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.6443 -2.5126 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.0323 -0.7500 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.0323 0.7500 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.5241 0.5932 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.3442 -2.2172 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.7707 -2.6807 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.0826 -4.1480 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.9679 -5.1517 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.5413 -4.6881 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.2294 -3.2209 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.5734 -5.6918 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 0.2615 -7.1591 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.2798 -6.6189 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.1650 -7.6226 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.3907 1.0037 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 7.8943 1.3846 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 5.6443 2.6836 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 6.3943 -1.2135 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 4.1443 1.5855 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 4.1443 -1.4145 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 2.6443 2.6836 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.1496 4.8695 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 0.9688 4.7585 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.3746 2.8945 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 2.6004 -0.7041 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 1.0283 -2.5730 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.5321 -0.7762 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.5207 2.1683 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.0159 0.4364 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.6809 2.0850 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.5503 -0.9066 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.8855 -1.6771 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.5092 -4.6115 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 1.2430 -2.9347 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 0.1309 -8.6534 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 1.7288 -7.4709 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.2375 -7.2115 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.1810 -8.7547 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.1687 -8.7373 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.4609 -6.2981 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 3.8870 0.8991 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 2 0 2 3 1 0 3 4 1 0 4 5 2 0 5 6 1 0 6 7 1 1 7 8 1 0 6 9 1 0 9 10 1 0 10 11 1 0 11 12 2 0 10 13 1 0 13 14 1 0 14 15 1 0 13 16 1 0 16 17 2 0 17 18 1 0 18 19 2 0 19 20 1 0 20 21 2 0 20 22 1 0 22 23 1 0 19 24 1 0 24 25 1 0 9 26 1 0 11 4 1 0 21 16 1 0 14 6 1 0 1 27 1 0 1 28 1 0 2 29 1 0 3 30 1 0 3 31 1 0 5 32 1 0 8 33 1 0 8 34 1 0 8 35 1 0 9 36 1 6 10 37 1 6 13 38 1 1 14 39 1 6 15 40 1 0 15 41 1 0 15 42 1 0 17 43 1 0 18 44 1 0 21 45 1 0 23 46 1 0 23 47 1 0 23 48 1 0 25 49 1 0 25 50 1 0 25 51 1 0 26 52 1 0 M END

Standard InCHIKey	YYEUHNBQISBESB-LOPMHCFQSA-N
Standard InCHI	InChI=1S/C21H26O5/c1-6-7-14-11-21(26-5)12(2)17(18(19(14)22)20(21)23)13-8-9-15(24-3)16(10-13)25-4/h6,8-12,17-18,20,23H,1,7H2,2-5H3/t12-,17+,18-,20+,21-/m1/s1
SMILES	C=CCC1=C[C@]2(OC)[C@H]([C@@H](C1=O)[C@@H]([C@H]2C)c1ccc(c(c1)OC)OC)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	358.18	Volume:	374.235 ? Van der Waals volume.
Dense:	0.957	LogP:	2.65 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	2.71 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-3.774 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	6.0	Rigid Bonds:	17.0
TPSA:	64.99 ? Topological Polar Surface Area.	H-Bond Acceptor:	5.0
H-Bond Donor:	1.0	Rings:	3.0
Heavy Atoms:	5.0

MedChem Properties

QED Drug-Likeness Score:	0.792	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	4.911	Fsp³:	0.476
MCE-18:	69.774 ? 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:	0
Colloidal aggregators:	0.069	Fluc inhibitor:	0.337 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.039 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.006 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.192	Promiscuous compounds:	0.318

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-4.793	MDCK Permeability:	-4.61
Pgp-inhibitor:	0.901	Pgp-substrate:	0.02
PAMPA:	0.067 ? 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):	0.711
20% Bioavailability (F20%):	0.545	30% Bioavailability (F30%):	0.984
50% Bioavailability (F50%):	0.994

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.01	MRP1:	0.407
Plasma Protein Binding (PPB):	74.315%	Volume Distribution (VD):	0.242
Fu:	26.909% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	1.0
OATP1B3 inhibitor:	1.0	BCRP inhibitor:	0.926
BSEP inhibitor:	0.718

ADMET: Metabolism

CYP1A2-inhibitor:	0.015	CYP1A2-substrate:	0.688
CYP2C19-inhibitor:	0.73	CYP2C19-substrate:	0.876
CYP2C9-inhibitor:	0.021	CYP2C9-substrate:	0.014
CYP2D6-inhibitor:	0.38	CYP2D6-substrate:	0.946
CYP3A4-inhibitor:	0.955	CYP3A4-substrate:	1.0
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	1.0
HLM stability:	0.927 ? 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):

7.155

Half-life (T1/2):

2.389

ADMET: Toxicity

hERG Blockers:	0.113	hERG Blockers (10um):	0.454
Human Hepatotoxicity (H-HT):	0.503	Drug-induced Liver Injury (DILI):	0.888
AMES Toxicity:	0.714	Rat Oral Acute Toxicity:	0.612
Maximum Recommended Daily Dose:	0.435	Skin Sensitization:	0.968
Carcinogencity:	0.605	Eye Corrosion:	0.001
Eye Irritation:	0.697	Respiratory Toxicity:	0.916
Drug-induced Neurotoxicity:	0.553	Ototoxicity:	0.656
Hematotoxicity:	0.693	Drug-induced Nephrotoxicity:	0.67
Genotoxicity:	0.933	RPMI-8226 Immunitoxicity:	0.215
A549 Cytotoxicity:	0.413	Hek293 Cytotoxicity:	0.499
BCF:	1.163 ? 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:	3.56 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.969 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.411 ? 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
NPO19526	Pleurothyrium cinereum	Species	Lauraceae	Eukaryota	leaves	n.a.	n.a.	PMID[19548690]
NPO26326	Ocotea macrophylla	Species	Lauraceae	Eukaryota	leaves	n.a.	n.a.	PMID[19880317]
NPO27964	Nectandra amazonum	Species	Lauraceae	Eukaryota	leaves	n.a.	n.a.	PMID[19880317]
NPO19526	Pleurothyrium cinereum	Species	Lauraceae	Eukaryota	leaves	n.a.	n.a.	PMID[19880317]
NPO26326	Ocotea macrophylla	Species	Lauraceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO26326	Ocotea macrophylla	Species	Lauraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO27964	Nectandra amazonum	Species	Lauraceae	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	6
Ratio IC50	1

Activity Type	# Activity
Individual protein	2
Others	2
Non-molecular	3

Molecular-level activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT324	Individual protein	Cyclooxygenase-1	Ovis aries	IC50	=	38700.0	nM	PMID[17190444]
NPT325	Individual protein	Cyclooxygenase-2	Ovis aries	IC50	=	312000.0	nM	PMID[23985009]

In vitro activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	IC50	=	2330.0	nM	PMID[19880317]
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	IC50	=	54600.0	nM	PMID[19880317]
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	IC50	>	999000.0	nM	PMID[19880317]
NPT2	Others	Unspecified	n.a.	IC50	=	117000.0	nM	PMID[22934671]
NPT2	Others	Unspecified	n.a.	Ratio IC50	=	0.124	n.a.	PMID[19222165]

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 NPC476338 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	5650
0.1-0.2	40089
0.2-0.3	4048
0.3-0.4	49
0.4-0.5	12
0.5-0.6	5
0.6-0.7	1
0.7-0.8	0
0.8-0.85	2
0.85-0.9	0
0.9-0.95	0
0.95-1	1

Similarity Score	Similarity Level	Natural Product ID
1.0	High Similarity	NPC476359
0.8246	Intermediate Similarity	NPC476364
0.8148	Intermediate Similarity	NPC476335
0.7333	Intermediate Similarity	NPC476337
0.6154	Remote Similarity	NPC484826
0.5556	Remote Similarity	NPC476362
0.5231	Remote Similarity	NPC476340
0.5231	Remote Similarity	NPC28724
0.5139	Remote Similarity	NPC484827
0.5072	Remote Similarity	NPC476336

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC476338 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	2539
0.1-0.2	6321
0.2-0.3	287
0.3-0.4	3
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