NPASS Compound

Natural Product: NPC470428

Natural Product ID	NPC470428
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	3Beta-Hydroxy-15-Nor-14-Oxo-8(17),12-Labdadien-14-Al
IUPAC Name	(E)-4-[(1S,4aR,6S,8aR)-6-hydroxy-5,5,8a-trimethyl-2-methylidene-3,4,4a,6,7,8-hexahydro-1H-naphthalen-1-yl]-2-methylbut-2-enal
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL2036049
PubChem CID	57409862
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000012] Lipids and lipid-like molecules [CHEMONTID:0000259] Prenol lipids [CHEMONTID:0001551] Diterpenoids

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 51 52 0 0 0 0 0 0 0 0999 V2000 4.0653 -0.0439 1.1393 C 0 0 0 0 0 0 0 0 0 0 0 0 3.7140 0.9284 0.0808 C 0 0 0 0 0 0 0 0 0 0 0 0 2.8788 0.5681 -0.8573 C 0 0 0 0 0 0 0 0 0 0 0 0 2.2187 -0.7471 -0.9852 C 0 0 0 0 0 0 0 0 0 0 0 0 0.7541 -0.7581 -1.1026 C 0 0 0 0 0 0 0 0 0 0 0 0 0.2988 -2.2008 -1.2360 C 0 0 0 0 0 0 0 0 0 0 0 0 1.1669 -3.1805 -1.3640 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.1410 -2.5487 -1.2278 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.0073 -1.6389 -0.4406 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.4792 -0.2238 -0.5182 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.0684 -0.2371 0.0521 C 0 0 0 0 0 0 0 0 0 0 0 0 0.3613 1.0698 0.5890 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.6633 1.8816 1.3108 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.0169 1.2831 1.4324 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.3931 0.7839 0.0668 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.3985 2.0389 -0.8185 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.8509 0.3073 0.0781 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.9106 2.3491 1.7081 O 0 0 0 0 0 0 0 0 0 0 0 0 0.0742 -1.2731 1.1508 C 0 0 0 0 0 0 0 0 0 0 0 0 4.3014 2.2610 0.1033 C 0 0 0 0 0 0 0 0 0 0 0 0 5.0963 2.5959 1.0007 O 0 0 0 0 0 0 0 0 0 0 0 0 4.3968 -0.9774 0.5972 H 0 0 0 0 0 0 0 0 0 0 0 0 4.8779 0.3303 1.7996 H 0 0 0 0 0 0 0 0 0 0 0 0 3.1807 -0.3232 1.7234 H 0 0 0 0 0 0 0 0 0 0 0 0 2.6505 1.2985 -1.6219 H 0 0 0 0 0 0 0 0 0 0 0 0 2.6046 -1.1905 -1.9611 H 0 0 0 0 0 0 0 0 0 0 0 0 2.6012 -1.4692 -0.2096 H 0 0 0 0 0 0 0 0 0 0 0 0 0.4692 -0.2069 -2.0361 H 0 0 0 0 0 0 0 0 0 0 0 0 2.2420 -3.0431 -1.3839 H 0 0 0 0 0 0 0 0 0 0 0 0 0.7512 -4.2046 -1.4558 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.2530 -3.5743 -0.8269 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.4715 -2.6116 -2.3008 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.0164 -1.6558 -0.9640 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.2450 -1.9852 0.5745 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.4525 -0.0128 -1.6332 H 0 0 0 0 0 0 0 0 0 0 0 0 0.8023 1.6881 -0.2022 H 0 0 0 0 0 0 0 0 0 0 0 0 1.1594 0.8733 1.3663 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.3501 2.1878 2.3521 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.7988 2.8794 0.7943 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.1660 0.5768 2.2454 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.7079 2.9293 -0.2354 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.1127 1.9052 -1.6563 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.3931 2.1631 -1.2835 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.9702 -0.6135 0.6540 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.1761 0.2229 -0.9768 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.4546 1.1288 0.5276 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.6993 2.0263 2.2170 H 0 0 0 0 0 0 0 0 0 0 0 0 0.9026 -0.9348 1.8105 H 0 0 0 0 0 0 0 0 0 0 0 0 0.3849 -2.2693 0.7785 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.8038 -1.3363 1.8191 H 0 0 0 0 0 0 0 0 0 0 0 0 4.0466 2.9832 -0.6743 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 2 3 3 4 1 0 4 5 1 0 5 6 1 0 6 7 2 0 6 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 1 0 15 16 1 0 15 17 1 0 14 18 1 0 11 19 1 0 2 20 1 0 20 21 2 0 11 5 1 0 15 10 1 0 1 22 1 0 1 23 1 0 1 24 1 0 3 25 1 0 4 26 1 0 4 27 1 0 5 28 1 0 7 29 1 0 7 30 1 0 8 31 1 0 8 32 1 0 9 33 1 0 9 34 1 0 10 35 1 0 12 36 1 0 12 37 1 0 13 38 1 0 13 39 1 0 14 40 1 0 16 41 1 0 16 42 1 0 16 43 1 0 17 44 1 0 17 45 1 0 17 46 1 0 18 47 1 0 19 48 1 0 19 49 1 0 19 50 1 0 20 51 1 0 M END

Standard InCHIKey	VIBIHOWJZCXZNF-WUWWUOSASA-N
Standard InCHI	InChI=1S/C19H30O2/c1-13(12-20)6-8-15-14(2)7-9-16-18(3,4)17(21)10-11-19(15,16)5/h6,12,15-17,21H,2,7-11H2,1,3-5H3/b13-6+/t15-,16-,17-,19+/m0/s1
SMILES	CC(=CCC1C(=C)CCC2C1(CCC(C2(C)C)O)C)C=O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	290.22	Volume:	329.738 ? Van der Waals volume.
Dense:	0.88	LogP:	3.548 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	3.493 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-3.996 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	3.0	Rigid Bonds:	14.0
TPSA:	37.3 ? Topological Polar Surface Area.	H-Bond Acceptor:	2.0
H-Bond Donor:	1.0	Rings:	2.0
Heavy Atoms:	2.0

MedChem Properties

QED Drug-Likeness Score:	0.478	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	4.255	Fsp³:	0.737
MCE-18:	43.273 ? 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:	Rejected
Golden Triangle Rule:	Rejected	BMS Rule:	1
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.062	Fluc inhibitor:	0.0 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.002 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.038 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.863	Promiscuous compounds:	0.01

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-4.559	MDCK Permeability:	-4.732
Pgp-inhibitor:	0.041	Pgp-substrate:	0.023
PAMPA:	0.393 ? 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):	0.034
20% Bioavailability (F20%):	0.046	30% Bioavailability (F30%):	0.087
50% Bioavailability (F50%):	0.96

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.767	MRP1:	0.91
Plasma Protein Binding (PPB):	73.426%	Volume Distribution (VD):	-0.172
Fu:	25.648% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.039
OATP1B3 inhibitor:	0.958	BCRP inhibitor:	0.061
BSEP inhibitor:	0.192

ADMET: Metabolism

CYP1A2-inhibitor:	0.108	CYP1A2-substrate:	0.156
CYP2C19-inhibitor:	0.934	CYP2C19-substrate:	0.048
CYP2C9-inhibitor:	0.451	CYP2C9-substrate:	0.001
CYP2D6-inhibitor:	0.663	CYP2D6-substrate:	0.013
CYP3A4-inhibitor:	0.029	CYP3A4-substrate:	0.001
CYP2B6-substrate:	0.427	CYP2C8-inhibitor:	0.193
HLM stability:	0.737 ? 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):

13.485

Half-life (T1/2):

1.083

ADMET: Toxicity

hERG Blockers:	0.078	hERG Blockers (10um):	0.587
Human Hepatotoxicity (H-HT):	0.384	Drug-induced Liver Injury (DILI):	0.084
AMES Toxicity:	0.287	Rat Oral Acute Toxicity:	0.432
Maximum Recommended Daily Dose:	0.816	Skin Sensitization:	0.72
Carcinogencity:	0.49	Eye Corrosion:	0.197
Eye Irritation:	0.858	Respiratory Toxicity:	0.864
Drug-induced Neurotoxicity:	0.657	Ototoxicity:	0.679
Hematotoxicity:	0.147	Drug-induced Nephrotoxicity:	0.115
Genotoxicity:	0.09	RPMI-8226 Immunitoxicity:	0.052
A549 Cytotoxicity:	0.311	Hek293 Cytotoxicity:	0.361
BCF:	1.893 ? 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:	4.549 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.997 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	5.416 ? 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
NPO21178	Chloranthus serratus	Species	Chloranthaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[19053511]
NPO21178	Chloranthus serratus	Species	Chloranthaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[22372956]
NPO21178	Chloranthus serratus	Species	Chloranthaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[27588583]
NPO21178	Chloranthus serratus	Species	Chloranthaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[30724564]
NPO21178	Chloranthus serratus	Species	Chloranthaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO21178	Chloranthus serratus	Species	Chloranthaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO21178	Chloranthus serratus	Species	Chloranthaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO21178	Chloranthus serratus	Species	Chloranthaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO21178	Chloranthus serratus	Species	Chloranthaceae	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 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
NPT113	Cell line	RAW264.7	Mus musculus	IC50	>	10000.0	nM	PMID[24215398]

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 NPC470428 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	17007
0.1-0.2	25017
0.2-0.3	6913
0.3-0.4	747
0.4-0.5	138
0.5-0.6	23
0.6-0.7	7
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
0.7826	Intermediate Similarity	NPC476949
0.7059	Intermediate Similarity	NPC478375
0.6458	Remote Similarity	NPC470429
0.625	Remote Similarity	NPC234974
0.6154	Remote Similarity	NPC482141
0.6154	Remote Similarity	NPC482142
0.6154	Remote Similarity	NPC608380
0.6071	Remote Similarity	NPC191521
0.6034	Remote Similarity	NPC325594
0.5893	Remote Similarity	NPC159763
0.5893	Remote Similarity	NPC278386
0.5893	Remote Similarity	NPC124512
0.5789	Remote Similarity	NPC72845
0.5763	Remote Similarity	NPC73038
0.5763	Remote Similarity	NPC10349
0.566	Remote Similarity	NPC281880
0.5652	Remote Similarity	NPC144650
0.5577	Remote Similarity	NPC175334
0.537	Remote Similarity	NPC48362
0.537	Remote Similarity	NPC99321
0.537	Remote Similarity	NPC608815
0.537	Remote Similarity	NPC610130
0.5246	Remote Similarity	NPC158393
0.5238	Remote Similarity	NPC73911
0.5192	Remote Similarity	NPC477138
0.5179	Remote Similarity	NPC310479
0.5179	Remote Similarity	NPC238146
0.5161	Remote Similarity	NPC607567
0.5161	Remote Similarity	NPC607574
0.5094	Remote Similarity	NPC169275
0.5094	Remote Similarity	NPC52449
0.5088	Remote Similarity	NPC79027

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC470428 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	6611
0.1-0.2	2368
0.2-0.3	163
0.3-0.4	7
0.4-0.5	0
0.5-0.6	1
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
0.5893	Remote Similarity	NPD4225	Phase 3

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