NPASS Compound

Natural Product: NPC470954

Natural Product ID	NPC470954
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	Withametelin
IUPAC Name	(1R,5S,8R)-8-[(8S,9S,10R,13S,14S,17R)-10,13-dimethyl-1-oxo-4,7,8,9,11,12,14,15,16,17-decahydrocyclopenta[a]phenanthren-17-yl]-5-methyl-4-methylidene-2,6-dioxabicyclo[3.3.1]nonan-3-one
Synonyms	Withametelin
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL2333167
PubChem CID	71718229
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000012] Lipids and lipid-like molecules [CHEMONTID:0000258] Steroids and steroid derivatives [CHEMONTID:0001125] Steroid lactones

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 68 73 0 0 0 0 0 0 0 0999 V2000 -0.9775 0.2678 -2.1974 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.2208 0.3964 -0.8627 C 0 0 0 0 0 0 0 0 0 0 0 0 0.1804 -0.9479 -0.3835 C 0 0 0 0 0 0 0 0 0 0 0 0 1.5401 -1.1632 0.1485 C 0 0 0 0 0 0 0 0 0 0 0 0 2.4229 0.0329 0.2002 C 0 0 0 0 0 0 0 0 0 0 0 0 2.2891 0.7632 -1.0807 C 0 0 0 0 0 0 0 0 0 0 0 0 0.9192 1.3396 -1.1915 C 0 0 0 0 0 0 0 0 0 0 0 0 0.7467 2.5952 -0.3640 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.7617 2.6110 -0.2114 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.9286 1.1249 0.1976 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.2180 0.8308 0.7510 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.5531 -0.4313 1.4344 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.7044 -0.1769 2.2355 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.8148 0.0236 1.4622 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.6619 1.3289 0.7178 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.3940 1.1842 -0.1535 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.6839 0.2279 -1.1230 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.5291 -0.8336 -0.9119 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.8452 -1.5999 -1.8204 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.0464 -1.0306 0.4282 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.7125 -2.1152 0.7490 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.0615 0.0525 2.3197 C 0 0 0 0 0 0 0 0 0 0 0 0 2.6462 -0.0553 -2.2623 C 0 0 0 0 0 0 0 0 0 0 0 0 3.9524 -0.7088 -2.0550 C 0 0 0 0 0 0 0 0 0 0 0 0 4.4958 -0.8382 -0.8800 C 0 0 0 0 0 0 0 0 0 0 0 0 3.8707 -0.3500 0.3554 C 0 0 0 0 0 0 0 0 0 0 0 0 4.1006 -1.2519 1.4983 C 0 0 0 0 0 0 0 0 0 0 0 0 3.4537 -1.0951 2.5464 O 0 0 0 0 0 0 0 0 0 0 0 0 5.0763 -2.3197 1.4061 C 0 0 0 0 0 0 0 0 0 0 0 0 5.8735 -2.4499 0.3469 C 0 0 0 0 0 0 0 0 0 0 0 0 5.8319 -1.5318 -0.8058 C 0 0 0 0 0 0 0 0 0 0 0 0 4.6039 0.9609 0.7076 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.1677 0.2307 -3.0032 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.4581 -0.6995 -2.3184 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.5277 1.1652 -2.4631 H 0 0 0 0 0 0 0 0 0 0 0 0 0.0365 -1.6741 -1.2456 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.5320 -1.3564 0.3714 H 0 0 0 0 0 0 0 0 0 0 0 0 1.5395 -1.5967 1.1957 H 0 0 0 0 0 0 0 0 0 0 0 0 2.1030 -1.9503 -0.4387 H 0 0 0 0 0 0 0 0 0 0 0 0 2.1920 0.7197 1.0440 H 0 0 0 0 0 0 0 0 0 0 0 0 2.9905 1.6326 -1.0574 H 0 0 0 0 0 0 0 0 0 0 0 0 0.8668 1.7269 -2.2560 H 0 0 0 0 0 0 0 0 0 0 0 0 1.2258 2.5083 0.6301 H 0 0 0 0 0 0 0 0 0 0 0 0 1.0271 3.5167 -0.9000 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.0041 3.2785 0.6109 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.2531 2.8171 -1.1607 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.1686 1.0929 1.0636 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.3966 1.6143 1.5943 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.8039 -0.7167 2.2372 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.8653 -1.2811 0.8279 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.5154 2.1200 1.4765 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.4875 1.5319 0.0377 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.2449 2.2137 -0.5753 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.8976 -2.8966 0.0263 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.1010 -2.2739 1.7374 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.2425 1.0661 2.7606 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.9264 -0.1438 1.6564 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.0457 -0.7373 3.0774 H 0 0 0 0 0 0 0 0 0 0 0 0 2.6499 0.5660 -3.1873 H 0 0 0 0 0 0 0 0 0 0 0 0 1.9233 -0.8903 -2.4618 H 0 0 0 0 0 0 0 0 0 0 0 0 4.4467 -1.0849 -2.9607 H 0 0 0 0 0 0 0 0 0 0 0 0 5.1831 -3.0552 2.2161 H 0 0 0 0 0 0 0 0 0 0 0 0 6.5727 -3.2742 0.3591 H 0 0 0 0 0 0 0 0 0 0 0 0 6.0166 -2.1164 -1.7257 H 0 0 0 0 0 0 0 0 0 0 0 0 6.5870 -0.7308 -0.7456 H 0 0 0 0 0 0 0 0 0 0 0 0 4.8497 1.5059 -0.2279 H 0 0 0 0 0 0 0 0 0 0 0 0 5.5677 0.7164 1.2051 H 0 0 0 0 0 0 0 0 0 0 0 0 3.9705 1.6148 1.3199 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 1 0 3 4 1 0 4 5 1 0 5 6 1 0 6 7 1 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 1 0 15 16 1 0 16 17 1 0 17 18 1 0 18 19 2 0 18 20 1 0 20 21 2 0 14 22 1 0 6 23 1 0 23 24 1 0 24 25 2 0 25 26 1 0 26 27 1 0 27 28 2 0 27 29 1 0 29 30 2 0 30 31 1 0 26 32 1 0 7 2 1 0 10 2 1 0 26 5 1 0 16 11 1 0 20 14 1 0 31 25 1 0 1 33 1 0 1 34 1 0 1 35 1 0 3 36 1 0 3 37 1 0 4 38 1 0 4 39 1 0 5 40 1 0 6 41 1 0 7 42 1 0 8 43 1 0 8 44 1 0 9 45 1 0 9 46 1 0 10 47 1 0 11 48 1 0 12 49 1 0 12 50 1 0 15 51 1 0 15 52 1 0 16 53 1 0 21 54 1 0 21 55 1 0 22 56 1 0 22 57 1 0 22 58 1 0 23 59 1 0 23 60 1 0 24 61 1 0 29 62 1 0 30 63 1 0 31 64 1 0 31 65 1 0 32 66 1 0 32 67 1 0 32 68 1 0 M END

Standard InCHIKey	QUGZOXCXHGEACS-FIPVAASQSA-N
Standard InCHI	InChI=1S/C28H36O4/c1-16-25(30)32-23-14-27(16,3)31-15-19(23)21-11-10-20-18-9-8-17-6-5-7-24(29)28(17,4)22(18)12-13-26(20,21)2/h5,7-8,18-23H,1,6,9-15H2,2-4H3/t18-,19-,20-,21+,22-,23+,26-,27-,28-/m0/s1
SMILES	CC12CCC3C(C1CCC2C4COC5(CC4OC(=O)C5=C)C)CC=C6C3(C(=O)C=CC6)C

Calculated Properties

Physi-Chem Properties

Molecular Weight:	436.26	Volume:	463.484 ? Van der Waals volume.
Dense:	0.941	LogP:	3.343 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	3.479 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-4.555 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	1.0	Rigid Bonds:	33.0
TPSA:	52.6 ? Topological Polar Surface Area.	H-Bond Acceptor:	4.0
H-Bond Donor:	0.0	Rings:	6.0
Heavy Atoms:	4.0

MedChem Properties

QED Drug-Likeness Score:	0.323	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	5.821	Fsp³:	0.714
MCE-18:	100.208 ? 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:	1
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.693	Fluc inhibitor:	0.021 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.026 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.252 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.343	Promiscuous compounds:	0.008

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-4.606	MDCK Permeability:	-4.762
Pgp-inhibitor:	0.071	Pgp-substrate:	0.001
PAMPA:	0.056 ? 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):	0.025
20% Bioavailability (F20%):	0.045	30% Bioavailability (F30%):	0.477
50% Bioavailability (F50%):	0.942

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.813	MRP1:	0.974
Plasma Protein Binding (PPB):	98.292%	Volume Distribution (VD):	0.214
Fu:	1.602% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.059
OATP1B3 inhibitor:	0.993	BCRP inhibitor:	0.0
BSEP inhibitor:	0.997

ADMET: Metabolism

CYP1A2-inhibitor:	0.516	CYP1A2-substrate:	0.118
CYP2C19-inhibitor:	0.789	CYP2C19-substrate:	0.009
CYP2C9-inhibitor:	0.376	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.017	CYP2D6-substrate:	0.171
CYP3A4-inhibitor:	0.013	CYP3A4-substrate:	0.002
CYP2B6-substrate:	0.988	CYP2C8-inhibitor:	0.975
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):

10.348

Half-life (T1/2):

1.224

ADMET: Toxicity

hERG Blockers:	0.079	hERG Blockers (10um):	0.325
Human Hepatotoxicity (H-HT):	0.685	Drug-induced Liver Injury (DILI):	0.655
AMES Toxicity:	0.358	Rat Oral Acute Toxicity:	0.373
Maximum Recommended Daily Dose:	0.977	Skin Sensitization:	0.607
Carcinogencity:	0.745	Eye Corrosion:	0.0
Eye Irritation:	0.058	Respiratory Toxicity:	0.275
Drug-induced Neurotoxicity:	0.682	Ototoxicity:	0.591
Hematotoxicity:	0.196	Drug-induced Nephrotoxicity:	0.164
Genotoxicity:	0.492	RPMI-8226 Immunitoxicity:	0.115
A549 Cytotoxicity:	0.145	Hek293 Cytotoxicity:	0.655
BCF:	1.734 ? 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:	4.892 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	6.512 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	5.864 ? 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
NPO22157	Datura wrightii	Species	Solanaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[23252848]
NPO22157	Datura wrightii	Species	Solanaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO22157	Datura wrightii	Species	Solanaceae	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
Ratio IC50	1
IC50	4

Activity Type	# Activity
Cell line	3
Non-molecular	2

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
NPT171	Cell line	MRC5	Homo sapiens	Ratio IC50	=	5.1	n.a.	PMID[23252848]
NPT171	Cell line	MRC5	Homo sapiens	IC50	=	5100.0	nM	PMID[19650652]
NPT380	Cell line	U-251	Homo sapiens	IC50	=	2200.0	nM	PMID[18183025]
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	IC50	=	2700.0	nM	PMID[23252848]
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	IC50	=	1000.0	nM	PMID[23252848]

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 NPC470954 and all remaining natural products in the NPASS database.
● The right table: Most similar natural products (Tc>=0.5 or Top200).

Similarity Score	Similarity Level	Natural Product ID

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC470954 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

Similarity Score	Similarity Level	Drug ID	Developmental Stage

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