NPASS Compound

Natural Product: NPC470978

Natural Product ID	NPC470978
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	((3S,3Ar,5R,7S,7As,E)-1-Ethylidene-7-Isopropyl-3-(2-Methylbutanoyloxy)-4-Methylene-2-Oxooctahydro-1H-Inden-5-Yl)3-Methylpent-2-Enoate
IUPAC Name	[(1E,3S,3aR,5R,7S,7aS)-1-ethylidene-3-(2-methylbutanoyloxy)-4-methylidene-2-oxo-7-propan-2-yl-3,3a,5,6,7,7a-hexahydroinden-5-yl] (E)-3-methylpent-2-enoate
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL2334777
PubChem CID	71718849
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000012] Lipids and lipid-like molecules [CHEMONTID:0000259] Prenol lipids [CHEMONTID:0001550] Sesquiterpenoids

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 69 70 0 0 0 0 0 0 0 0999 V2000 -6.0125 -3.9471 -0.3765 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.2295 -2.7023 0.4566 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.9825 -1.8919 0.3998 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.3486 -1.6311 1.5261 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.1369 -0.8530 1.5419 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.5757 -0.6361 2.6468 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.5291 -0.3170 0.4367 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.3182 0.4555 0.4923 C 0 0 2 0 0 0 0 0 0 0 0 0 -1.5707 1.7504 -0.1718 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.3175 2.3777 -0.8351 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.3735 3.8495 -0.8635 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.6599 4.1866 -1.6630 C 0 0 0 0 0 0 0 0 0 0 0 0 0.7496 4.3479 -1.7575 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8040 1.6609 -0.2439 C 0 0 2 0 0 0 0 0 0 0 0 0 2.1674 2.0332 -0.3356 C 0 0 0 0 0 0 0 0 0 0 0 0 2.8521 2.9758 0.2717 C 0 0 0 0 0 0 0 0 0 0 0 0 2.2470 3.9094 1.2680 C 0 0 0 0 0 0 0 0 0 0 0 0 2.8216 1.0791 -1.2612 C 0 0 0 0 0 0 0 0 0 0 0 0 3.7864 1.2312 -2.0280 O 0 0 0 0 0 0 0 0 0 0 0 0 2.0661 -0.2361 -1.1183 C 0 0 2 0 0 0 0 0 0 0 0 0 0.7135 0.2792 -0.9542 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.2953 -0.4316 -0.1910 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.3705 -1.7515 -0.0641 C 0 0 0 0 0 0 0 0 0 0 0 0 2.6051 -0.9695 -0.0438 O 0 0 0 0 0 0 0 0 0 0 0 0 3.2342 -2.2038 -0.1825 C 0 0 0 0 0 0 0 0 0 0 0 0 3.3054 -2.6569 -1.3523 O 0 0 0 0 0 0 0 0 0 0 0 0 3.7985 -2.9774 0.9201 C 0 0 0 0 0 0 0 0 0 0 0 0 2.7900 -3.3597 1.9698 C 0 0 0 0 0 0 0 0 0 0 0 0 4.9707 -2.2254 1.5609 C 0 0 0 0 0 0 0 0 0 0 0 0 6.0632 -1.9719 0.5673 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.4620 -1.3873 -0.8915 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.2834 -3.6951 -1.1699 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.9888 -4.2529 -0.8079 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.6181 -4.7891 0.2405 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.4823 -2.9336 1.5036 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.0532 -2.1392 -0.0297 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.7736 -2.0247 2.4435 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.0496 0.4894 1.5539 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.4102 1.7088 -0.8658 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.8190 2.5046 0.6331 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.4487 2.0561 -1.9180 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.4903 4.3866 0.0707 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.6125 5.2239 -2.0305 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.5514 4.0647 -1.0188 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.7742 3.4922 -2.5158 H 0 0 0 0 0 0 0 0 0 0 0 0 1.3901 3.5188 -2.1394 H 0 0 0 0 0 0 0 0 0 0 0 0 0.3580 4.8229 -2.7081 H 0 0 0 0 0 0 0 0 0 0 0 0 1.3166 5.1669 -1.2759 H 0 0 0 0 0 0 0 0 0 0 0 0 0.5709 1.4984 0.8656 H 0 0 0 0 0 0 0 0 0 0 0 0 3.9207 3.1374 0.0807 H 0 0 0 0 0 0 0 0 0 0 0 0 2.8414 3.9205 2.2108 H 0 0 0 0 0 0 0 0 0 0 0 0 2.3102 4.9233 0.8485 H 0 0 0 0 0 0 0 0 0 0 0 0 1.2220 3.6690 1.5421 H 0 0 0 0 0 0 0 0 0 0 0 0 2.1847 -0.7358 -2.0996 H 0 0 0 0 0 0 0 0 0 0 0 0 0.2627 0.4240 -1.9919 H 0 0 0 0 0 0 0 0 0 0 0 0 0.3697 -2.3560 -0.5608 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.1611 -2.1887 0.5262 H 0 0 0 0 0 0 0 0 0 0 0 0 4.2337 -3.9168 0.5306 H 0 0 0 0 0 0 0 0 0 0 0 0 2.2562 -4.2928 1.6623 H 0 0 0 0 0 0 0 0 0 0 0 0 3.3568 -3.6171 2.8891 H 0 0 0 0 0 0 0 0 0 0 0 0 2.1004 -2.5435 2.2277 H 0 0 0 0 0 0 0 0 0 0 0 0 5.4005 -2.8441 2.3766 H 0 0 0 0 0 0 0 0 0 0 0 0 4.6050 -1.2690 1.9517 H 0 0 0 0 0 0 0 0 0 0 0 0 6.0900 -0.8789 0.2999 H 0 0 0 0 0 0 0 0 0 0 0 0 5.8989 -2.5120 -0.3657 H 0 0 0 0 0 0 0 0 0 0 0 0 7.0801 -2.1709 1.0020 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.4638 -1.8369 -1.0618 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.1656 -1.7288 -1.6955 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.4157 -0.2684 -0.9282 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 1 0 3 4 2 0 4 5 1 0 5 6 2 0 5 7 1 0 7 8 1 0 8 9 1 0 9 10 1 0 10 11 1 0 11 12 1 0 11 13 1 0 10 14 1 0 14 15 1 0 15 16 2 0 16 17 1 0 15 18 1 0 18 19 2 0 18 20 1 0 20 21 1 0 21 22 1 0 22 23 2 0 20 24 1 0 24 25 1 0 25 26 2 0 25 27 1 0 27 28 1 0 27 29 1 0 29 30 1 0 3 31 1 0 22 8 1 0 21 14 1 0 1 32 1 0 1 33 1 0 1 34 1 0 2 35 1 0 2 36 1 0 4 37 1 0 8 38 1 1 9 39 1 0 9 40 1 0 10 41 1 6 11 42 1 0 12 43 1 0 12 44 1 0 12 45 1 0 13 46 1 0 13 47 1 0 13 48 1 0 14 49 1 1 16 50 1 0 17 51 1 0 17 52 1 0 17 53 1 0 20 54 1 6 21 55 1 6 23 56 1 0 23 57 1 0 27 58 1 0 28 59 1 0 28 60 1 0 28 61 1 0 29 62 1 0 29 63 1 0 30 64 1 0 30 65 1 0 30 66 1 0 31 67 1 0 31 68 1 0 31 69 1 0 M END

Standard InCHIKey	XTQQLVJPORCMAK-OGWQZUEXSA-N
Standard InCHI	InChI=1S/C26H38O5/c1-9-15(6)12-21(27)30-20-13-19(14(4)5)23-18(11-3)24(28)25(22(23)17(20)8)31-26(29)16(7)10-2/h11-12,14,16,19-20,22-23,25H,8-10,13H2,1-7H3/b15-12+,18-11+/t16?,19-,20+,22-,23-,25-/m0/s1
SMILES	CC/C(=C/C(=O)O[C@@H]1C[C@@H](C(C)C)[C@@H]2/C(=CC)/C(=O)[C@H]([C@H]2C1=C)OC(=O)C(C)CC)/C

Calculated Properties

Physi-Chem Properties

Molecular Weight:	430.27	Volume:	469.272 ? Van der Waals volume.
Dense:	0.917	LogP:	5.154 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	4.38 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-5.466 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	9.0	Rigid Bonds:	16.0
TPSA:	69.67 ? Topological Polar Surface Area.	H-Bond Acceptor:	5.0
H-Bond Donor:	0.0	Rings:	2.0
Heavy Atoms:	5.0

MedChem Properties

QED Drug-Likeness Score:	0.315	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	5.005	Fsp³:	0.654
MCE-18:	43.302 ? 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:	0.69	Fluc inhibitor:	0.002 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.012 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.027 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.429	Promiscuous compounds:	0.253

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-4.864	MDCK Permeability:	-4.697
Pgp-inhibitor:	0.995	Pgp-substrate:	0.568
PAMPA:	0.002 ? 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):	0.002
20% Bioavailability (F20%):	0.62	30% Bioavailability (F30%):	0.931
50% Bioavailability (F50%):	0.993

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.001	MRP1:	0.942
Plasma Protein Binding (PPB):	96.194%	Volume Distribution (VD):	0.132
Fu:	3.704% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.994
OATP1B3 inhibitor:	0.91	BCRP inhibitor:	0.015
BSEP inhibitor:	1.0

ADMET: Metabolism

CYP1A2-inhibitor:	0.315	CYP1A2-substrate:	0.778
CYP2C19-inhibitor:	0.222	CYP2C19-substrate:	0.217
CYP2C9-inhibitor:	0.0	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.251
CYP3A4-inhibitor:	0.904	CYP3A4-substrate:	0.682
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.994
HLM stability:	0.967 ? 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):

7.417

Half-life (T1/2):

0.587

ADMET: Toxicity

hERG Blockers:	0.048	hERG Blockers (10um):	0.218
Human Hepatotoxicity (H-HT):	0.751	Drug-induced Liver Injury (DILI):	0.83
AMES Toxicity:	0.355	Rat Oral Acute Toxicity:	0.287
Maximum Recommended Daily Dose:	0.651	Skin Sensitization:	0.97
Carcinogencity:	0.693	Eye Corrosion:	0.006
Eye Irritation:	0.181	Respiratory Toxicity:	0.457
Drug-induced Neurotoxicity:	0.59	Ototoxicity:	0.649
Hematotoxicity:	0.642	Drug-induced Nephrotoxicity:	0.9
Genotoxicity:	0.687	RPMI-8226 Immunitoxicity:	0.334
A549 Cytotoxicity:	0.377	Hek293 Cytotoxicity:	0.393
BCF:	1.962 ? 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:	4.676 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	6.292 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	5.918 ? 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
NPO523	Tussilago farfara	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	PMID[10543912]
NPO5813	Ligularia songarica	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	PMID[23043462]
NPO523	Tussilago farfara	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	PMID[32881525]
NPO523	Tussilago farfara	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO5813	Ligularia songarica	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO523	Tussilago farfara	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO523	Tussilago farfara	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO523	Tussilago farfara	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO523	Tussilago farfara	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO5813	Ligularia songarica	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO523	Tussilago farfara	Species	Asteraceae	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
EC50	4
IC50	1

Activity Type	# Activity
Cell line	4
Non-molecular	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
NPT91	Cell line	KB	Homo sapiens	EC50	=	4.3	ug.mL-1	PubChem BioAssay data set
NPT83	Cell line	MCF7	Homo sapiens	EC50	=	4.0	ug.mL-1	PubChem BioAssay data set
NPT81	Cell line	A549	Homo sapiens	EC50	=	5.2	ug.mL-1	PubChem BioAssay data set
NPT82	Cell line	MDA-MB-231	Homo sapiens	IC50	=	13800.0	nM	PMID[32881525]
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	EC50	=	3.3	ug.mL-1	PMID[23043462]

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 NPC470978 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	23513
0.1-0.2	24915
0.2-0.3	1403
0.3-0.4	14
0.4-0.5	3
0.5-0.6	6
0.6-0.7	2
0.7-0.8	0
0.8-0.85	1
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	NPC486408
0.8039	Intermediate Similarity	NPC470974
0.6207	Remote Similarity	NPC486411
0.6207	Remote Similarity	NPC486407
0.5932	Remote Similarity	NPC486412
0.5902	Remote Similarity	NPC471934
0.5818	Remote Similarity	NPC486405
0.5818	Remote Similarity	NPC223192
0.5714	Remote Similarity	NPC486409
0.5072	Remote Similarity	NPC486413

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC470978 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	7194
0.1-0.2	1936
0.2-0.3	20
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