NPASS Compound

Natural Product: NPC527851

Natural Product ID	NPC527851
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	3beta-Acetoxytropane
IUPAC Name	[(1~{R},5~{S})-8-methyl-8-azabicyclo[3.2.1]octan-3-yl] acetate
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	n.a.
PubChem CID	n.a.
Chemical Classification	CHEMONTID:0000000 [Organic compounds]

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 30 31 0 0 0 0 0 0 0 0999 V2000 4.6031 -0.0408 0.7859 C 0 0 0 0 0 0 0 0 0 0 0 0 3.3565 0.0664 -0.0360 C 0 0 0 0 0 0 0 0 0 0 0 0 3.4483 0.3139 -1.2586 O 0 0 0 0 0 0 0 0 0 0 0 0 2.1004 -0.0984 0.5067 O 0 0 0 0 0 0 0 0 0 0 0 0 0.9008 0.0029 -0.2748 C 0 0 2 0 0 0 0 0 0 0 0 0 0.0871 1.0993 0.2876 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.3490 0.8241 0.5006 C 0 0 1 0 0 0 0 0 0 0 0 0 -2.0951 0.9694 -0.8302 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.6305 -0.3157 -1.5257 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.2580 -1.2331 -0.3779 C 0 0 1 0 0 0 0 0 0 0 0 0 0.2700 -1.3413 -0.2942 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.6384 -0.5432 0.8401 N 0 0 0 0 0 0 0 0 0 0 0 0 -2.9888 -0.7509 1.2284 C 0 0 0 0 0 0 0 0 0 0 0 0 4.5584 -0.9050 1.4791 H 0 0 0 0 0 0 0 0 0 0 0 0 4.7950 0.9110 1.3040 H 0 0 0 0 0 0 0 0 0 0 0 0 5.4559 -0.2285 0.1038 H 0 0 0 0 0 0 0 0 0 0 0 0 1.2403 0.2279 -1.3282 H 0 0 0 0 0 0 0 0 0 0 0 0 0.5083 1.4949 1.2580 H 0 0 0 0 0 0 0 0 0 0 0 0 0.1664 1.9849 -0.4102 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.7833 1.5639 1.1769 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.8067 1.8665 -1.3725 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.1797 0.8589 -0.6473 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.3997 -0.7323 -2.1811 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.6982 -0.0255 -2.0821 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.7228 -2.2092 -0.4980 H 0 0 0 0 0 0 0 0 0 0 0 0 0.4558 -1.9182 0.6555 H 0 0 0 0 0 0 0 0 0 0 0 0 0.6423 -1.9871 -1.1168 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.5415 -1.2713 0.4233 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.5081 0.1606 1.5785 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.9889 -1.4584 2.1052 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 9 10 1 0 10 11 1 0 10 12 1 0 12 13 1 0 11 5 1 0 12 7 1 0 1 14 1 0 1 15 1 0 1 16 1 0 5 17 1 6 6 18 1 0 6 19 1 0 7 20 1 1 8 21 1 0 8 22 1 0 9 23 1 0 9 24 1 0 10 25 1 6 11 26 1 0 11 27 1 0 13 28 1 0 13 29 1 0 13 30 1 0 M END

Standard InCHIKey	MDIDMOWWLBGYPG-ILWJIGKKSA-N
Standard InCHI	InChI=1S/C10H17NO2/c1-7(12)13-10-5-8-3-4-9(6-10)11(8)2/h8-10H,3-6H2,1-2H3/t8-,9+,10-
SMILES	CC(=O)O[C@@H]1C[C@H]2CC[C@@H](C1)N2C

Calculated Properties

Physi-Chem Properties

Molecular Weight:	183.13	Volume:	190.344 ? Van der Waals volume.
Dense:	0.962	LogP:	0.976 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	0.632 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-0.274 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	2.0	Rigid Bonds:	10.0
TPSA:	29.54 ? Topological Polar Surface Area.	H-Bond Acceptor:	3.0
H-Bond Donor:	0.0	Rings:	2.0
Heavy Atoms:	3.0

MedChem Properties

QED Drug-Likeness Score:	0.572	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	3.943	Fsp³:	0.9
MCE-18:	30.105 ? 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:	Accepted	BMS Rule:	0
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.404	Fluc inhibitor:	0.0 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.037 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.0 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.372	Promiscuous compounds:	0.839

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-4.743	MDCK Permeability:	-4.532
Pgp-inhibitor:	0.001	Pgp-substrate:	0.461
PAMPA:	0.203 ? 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):	0.0
20% Bioavailability (F20%):	0.0	30% Bioavailability (F30%):	0.009
50% Bioavailability (F50%):	0.115

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.914	MRP1:	0.54
Plasma Protein Binding (PPB):	25.413%	Volume Distribution (VD):	0.536
Fu:	76.436% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.892
OATP1B3 inhibitor:	0.189	BCRP inhibitor:	0.002
BSEP inhibitor:	0.0

ADMET: Metabolism

CYP1A2-inhibitor:	0.0	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	1.0	CYP2C19-substrate:	0.0
CYP2C9-inhibitor:	0.486	CYP2C9-substrate:	0.772
CYP2D6-inhibitor:	0.254	CYP2D6-substrate:	0.0
CYP3A4-inhibitor:	0.742	CYP3A4-substrate:	0.646
CYP2B6-substrate:	0.001	CYP2C8-inhibitor:	0.054
HLM stability:	0.479 ? 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):

9.555

Half-life (T1/2):

2.161

ADMET: Toxicity

hERG Blockers:	0.147	hERG Blockers (10um):	0.457
Human Hepatotoxicity (H-HT):	0.688	Drug-induced Liver Injury (DILI):	0.345
AMES Toxicity:	0.855	Rat Oral Acute Toxicity:	0.48
Maximum Recommended Daily Dose:	0.803	Skin Sensitization:	0.969
Carcinogencity:	0.531	Eye Corrosion:	0.673
Eye Irritation:	0.813	Respiratory Toxicity:	0.741
Drug-induced Neurotoxicity:	0.871	Ototoxicity:	0.368
Hematotoxicity:	0.353	Drug-induced Nephrotoxicity:	0.761
Genotoxicity:	0.665	RPMI-8226 Immunitoxicity:	0.098
A549 Cytotoxicity:	0.198	Hek293 Cytotoxicity:	0.179
BCF:	0.312 ? 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:	2.632 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	3.834 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	3.372 ? 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
NPO58780	Datura metel L.var.fastuosa(Bernh.)Danert	Genus	Solanaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO60926	Solandra macrocantha Dun	Genus	Solanaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO60464	Solandra hirsuta Dun	Genus	Solanaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO54571	Solandra guttata D.Don ex Lindley	Genus	Solanaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO51477	Solandra grandiflora Sw.	Genus	Solanaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO51443	Physalis peruviana L.	Genus	Solanaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO42868	Merremia tridentata	Species	Convolvulaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO62239	Hyoscyamus desertorum Tackh	Genus	Solanaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO59961	Grammosolen dixonii (F.Muell.et R.Tate)Haegi	Genus	Solanaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO63832	Datura wrightii Regel	Genus	Solanaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO50735	Datura suaveolens H.and B.ex Willd	Genus	Solanaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO46513	Datura sanguinea Ruiz.et Pav.	Genus	Solanaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO57245	Datura sanguinea R.and P.	Genus	Solanaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO57711	Datura quercifolia H.B.K.	Genus	Solanaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO63689	Hyoscyamus albus L.	Genus	Solanaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO47069	Datura metel L.var.fastuga	Genus	Solanaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO43053	Datura ferox L.	Genus	Solanaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO44202	Datura discolor Bernh	Genus	Solanaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO62396	Anthotroche walcottii F.Muell	Genus	Solanaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO56264	Anthotroche myoporoides C.A.Gardn	Genus	Solanaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO48328	Hyoscyamus pusillus L.	Genus	Solanaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO53998	Datura candida X candida	Genus	Solanaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO52483	Duboisia myoporoides R.Br.	Genus	Cyathocotylidae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO56699	Datura innoxia Mill	Genus	Solanaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO52892	Cyphanthera albicans (A.Cunn.) Miers ssp.albicans	Genus	Solanaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO49709	Bruguiera sexangula (Lour.) poir.	Genus	Rhizophoraceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO53820	Bruguiera exaristata Ding Hou	Genus	Rhizophoraceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO60205	Datura stramonium L.	Genus	Solanaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]

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 NPC527851 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	30894
0.1-0.2	18352
0.2-0.3	578
0.3-0.4	21
0.4-0.5	7
0.5-0.6	1
0.6-0.7	1
0.7-0.8	0
0.8-0.85	0
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	NPC319991
0.6364	Remote Similarity	NPC601708
0.5238	Remote Similarity	NPC65310

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC527851 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	6751
0.1-0.2	2294
0.2-0.3	72
0.3-0.4	23
0.4-0.5	5
0.5-0.6	2
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
0.5238	Remote Similarity	NPD2160	Phase 4
0.5116	Remote Similarity	NPD2159	Approved

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