NPASS Compound

Natural Product: NPC476850

Natural Product ID	NPC476850
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	methyl 2-[(1R,2R,4S,7S,8S,10S,11R,12R,13R,16R)-7-(furan-3-yl)-10-hydroxy-1,8,12,15,15-pentamethyl-5,18-dioxo-3,6,14-trioxapentacyclo[9.7.0.02,4.02,8.012,16]octadecan-13-yl]acetate
IUPAC Name	methyl 2-[(1R,2R,4S,7S,8S,10S,11R,12R,13R,16R)-7-(furan-3-yl)-10-hydroxy-1,8,12,15,15-pentamethyl-5,18-dioxo-3,6,14-trioxapentacyclo[9.7.0.02,4.02,8.012,16]octadecan-13-yl]acetate
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	n.a.
PubChem CID	86302631
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 70 75 0 0 0 0 0 0 0 0999 V2000 -1.8343 -2.0470 0.1083 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.1769 -0.5534 0.1410 C 0 0 1 0 0 0 0 0 0 0 0 0 -1.6720 0.1272 1.3591 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.1678 0.4048 1.3919 C 0 0 1 0 0 0 0 0 0 0 0 0 0.3448 0.4127 0.0059 C 0 0 2 0 0 0 0 0 0 0 0 0 1.6968 0.7771 -0.3336 C 0 0 2 0 0 0 0 0 0 0 0 0 1.8375 0.4257 -1.8331 C 0 0 1 0 0 0 0 0 0 0 0 0 1.3129 1.5521 -2.5970 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.1362 1.4976 -2.2444 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.9311 1.7819 -3.1006 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.6501 1.1181 -0.9150 C 0 0 1 0 0 0 0 0 0 0 0 0 -1.7771 0.1246 -1.1489 C 0 0 1 0 0 0 0 0 0 0 0 0 -2.3106 -0.4102 -2.2634 C 0 0 2 0 0 0 0 0 0 0 0 0 -2.8224 0.8350 -1.8793 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.3073 -1.4991 -1.9964 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.4356 -2.4412 -2.8187 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.0897 -1.4540 -0.8254 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.6935 -0.4951 0.1682 C 0 0 1 0 0 0 0 0 0 0 0 0 -4.3014 -0.7395 1.4642 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.4825 -1.9171 2.1398 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.0835 -1.6625 3.3013 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.3104 -0.3870 3.4335 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.8273 0.2379 2.2844 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.3024 2.3501 -0.3745 C 0 0 0 0 0 0 0 0 0 0 0 0 3.2018 -0.0763 -2.0590 C 0 0 0 0 0 0 0 0 0 0 0 0 3.3451 -0.7925 -0.8795 O 0 0 0 0 0 0 0 0 0 0 0 0 2.9733 0.2605 0.0760 C 0 0 2 0 0 0 0 0 0 0 0 0 3.3737 -0.2227 1.3959 C 0 0 0 0 0 0 0 0 0 0 0 0 2.7311 -1.4317 1.9285 C 0 0 0 0 0 0 0 0 0 0 0 0 2.0072 -2.1646 1.1771 O 0 0 0 0 0 0 0 0 0 0 0 0 2.8454 -1.8671 3.2305 O 0 0 0 0 0 0 0 0 0 0 0 0 2.2028 -3.0487 3.7048 C 0 0 0 0 0 0 0 0 0 0 0 0 3.2005 -1.1870 -3.1387 C 0 0 0 0 0 0 0 0 0 0 0 0 4.2853 0.8389 -2.3970 C 0 0 0 0 0 0 0 0 0 0 0 0 1.8289 2.3155 -0.1763 C 0 0 0 0 0 0 0 0 0 0 0 0 0.0258 1.5253 2.1712 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.7300 -2.6968 0.0733 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.2968 -2.3232 -0.8496 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.2631 -2.3593 1.0067 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.2611 1.0296 1.6326 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.9542 -0.5822 2.2127 H 0 0 0 0 0 0 0 0 0 0 0 0 0.2240 -0.4284 1.9989 H 0 0 0 0 0 0 0 0 0 0 0 0 0.2691 -0.6709 -0.2556 H 0 0 0 0 0 0 0 0 0 0 0 0 1.1920 -0.4488 -2.0863 H 0 0 0 0 0 0 0 0 0 0 0 0 1.3661 1.2749 -3.6963 H 0 0 0 0 0 0 0 0 0 0 0 0 1.7749 2.5296 -2.4927 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.8573 -0.4249 -3.2709 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.9930 0.4832 -0.2815 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.2245 -2.9293 1.8750 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.7848 0.0746 4.2830 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.8973 1.3081 2.1495 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.2148 3.2430 -1.0877 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.4364 2.2797 -0.3342 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.9888 2.7480 0.5666 H 0 0 0 0 0 0 0 0 0 0 0 0 3.7667 1.0059 -0.2430 H 0 0 0 0 0 0 0 0 0 0 0 0 3.3336 0.5383 2.2084 H 0 0 0 0 0 0 0 0 0 0 0 0 4.4854 -0.4773 1.4059 H 0 0 0 0 0 0 0 0 0 0 0 0 1.1947 -2.8608 4.0833 H 0 0 0 0 0 0 0 0 0 0 0 0 2.2589 -3.7983 2.8942 H 0 0 0 0 0 0 0 0 0 0 0 0 2.7995 -3.4840 4.5593 H 0 0 0 0 0 0 0 0 0 0 0 0 2.7488 -0.7219 -4.0403 H 0 0 0 0 0 0 0 0 0 0 0 0 4.2068 -1.5717 -3.3011 H 0 0 0 0 0 0 0 0 0 0 0 0 2.4887 -1.9978 -2.8393 H 0 0 0 0 0 0 0 0 0 0 0 0 4.2050 1.8934 -2.1834 H 0 0 0 0 0 0 0 0 0 0 0 0 4.5024 0.7790 -3.5062 H 0 0 0 0 0 0 0 0 0 0 0 0 5.2401 0.4441 -1.9382 H 0 0 0 0 0 0 0 0 0 0 0 0 2.8149 2.6825 -0.4396 H 0 0 0 0 0 0 0 0 0 0 0 0 1.7539 2.4641 0.9404 H 0 0 0 0 0 0 0 0 0 0 0 0 1.0700 2.8890 -0.6472 H 0 0 0 0 0 0 0 0 0 0 0 0 0.3057 1.3480 3.1024 H 0 0 0 0 0 0 0 0 0 0 0 0 2 1 1 6 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 2 0 9 11 1 0 11 12 1 0 12 13 1 0 13 14 1 0 13 15 1 0 15 16 2 0 15 17 1 0 17 18 1 0 18 19 1 0 19 20 2 0 20 21 1 0 21 22 1 0 22 23 2 0 11 24 1 1 7 25 1 0 25 26 1 0 26 27 1 0 27 28 1 0 28 29 1 0 29 30 2 0 29 31 1 0 31 32 1 0 25 33 1 0 25 34 1 0 6 35 1 6 4 36 1 0 12 2 1 0 18 2 1 0 11 5 1 0 27 6 1 0 12 14 1 1 23 19 1 0 1 37 1 0 1 38 1 0 1 39 1 0 3 40 1 0 3 41 1 0 4 42 1 1 5 43 1 6 7 44 1 1 8 45 1 0 8 46 1 0 13 47 1 6 18 48 1 6 20 49 1 0 22 50 1 0 23 51 1 0 24 52 1 0 24 53 1 0 24 54 1 0 27 55 1 6 28 56 1 0 28 57 1 0 32 58 1 0 32 59 1 0 32 60 1 0 33 61 1 0 33 62 1 0 33 63 1 0 34 64 1 0 34 65 1 0 34 66 1 0 35 67 1 0 35 68 1 0 35 69 1 0 36 70 1 0 M END

Standard InCHIKey	SQTDQWTYVSNTOG-WJQCSXITSA-N
Standard InCHI	InChI=1S/C27H34O9/c1-23(2)15-9-16(29)26(5)19(25(15,4)17(35-23)10-18(30)32-6)14(28)11-24(3)20(13-7-8-33-12-13)34-22(31)21-27(24,26)36-21/h7-8,12,14-15,17,19-21,28H,9-11H2,1-6H3/t14-,15-,17+,19+,20-,21+,24-,25+,26+,27+/m0/s1
SMILES	C[C@@]12C[C@@H]([C@@H]3[C@@]4([C@@H](CC(=O)[C@]3([C@@]15[C@H](O5)C(=O)O[C@H]2C6=COC=C6)C)C(O[C@@H]4CC(=O)OC)(C)C)C)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	502.22	Volume:	490.139 ? Van der Waals volume.
Dense:	1.025	LogP:	1.199 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	1.497 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-3.256 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	4.0	Rigid Bonds:	30.0
TPSA:	124.8 ? Topological Polar Surface Area.	H-Bond Acceptor:	9.0
H-Bond Donor:	1.0	Rings:	6.0
Heavy Atoms:	9.0

MedChem Properties

QED Drug-Likeness Score:	0.491	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	5.871	Fsp³:	0.741
MCE-18:	195.787 ? 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:	Accepted
Golden Triangle Rule:	Accepted	BMS Rule:	0
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.469	Fluc inhibitor:	0.009 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.014 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.008 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.049	Promiscuous compounds:	0.175

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.317	MDCK Permeability:	-5.011
Pgp-inhibitor:	0.5	Pgp-substrate:	0.172
PAMPA:	0.896 ? 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):	0.011
20% Bioavailability (F20%):	0.082	30% Bioavailability (F30%):	0.087
50% Bioavailability (F50%):	0.39

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.1	MRP1:	0.98
Plasma Protein Binding (PPB):	78.869%	Volume Distribution (VD):	-0.164
Fu:	20.695% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.971
OATP1B3 inhibitor:	0.915	BCRP inhibitor:	0.047
BSEP inhibitor:	0.966

ADMET: Metabolism

CYP1A2-inhibitor:	0.001	CYP1A2-substrate:	0.001
CYP2C19-inhibitor:	0.222	CYP2C19-substrate:	0.002
CYP2C9-inhibitor:	0.007	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.281
CYP3A4-inhibitor:	0.047	CYP3A4-substrate:	0.056
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.618
HLM stability:	0.292 ? 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):

8.567

Half-life (T1/2):

1.816

ADMET: Toxicity

hERG Blockers:	0.043	hERG Blockers (10um):	0.372
Human Hepatotoxicity (H-HT):	0.588	Drug-induced Liver Injury (DILI):	0.673
AMES Toxicity:	0.579	Rat Oral Acute Toxicity:	0.88
Maximum Recommended Daily Dose:	0.955	Skin Sensitization:	0.942
Carcinogencity:	0.458	Eye Corrosion:	0.006
Eye Irritation:	0.931	Respiratory Toxicity:	0.796
Drug-induced Neurotoxicity:	0.455	Ototoxicity:	0.697
Hematotoxicity:	0.44	Drug-induced Nephrotoxicity:	0.895
Genotoxicity:	0.974	RPMI-8226 Immunitoxicity:	0.273
A549 Cytotoxicity:	0.003	Hek293 Cytotoxicity:	0.023
BCF:	0.519 ? 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:	3.258 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.143 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.443 ? 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
NPO33678	Clausena emarginata	Species	Rutaceae	Eukaryota	stems	Xishuangbanna, Yunnan Province, China	2010-AUG	PMID[24593150]

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

Activity Type	# Activity
Cell line	4
Others	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
NPT393	Cell line	HCT-116	Homo sapiens	IC50	>	10000	nM	PMID[24593150]
NPT65	Cell line	HepG2	Homo sapiens	IC50	>	10000	nM	PMID[24593150]
NPT1820	Cell line	NCI-H1650	Homo sapiens	IC50	>	10000	nM	PMID[24593150]
NPT146	Cell line	SK-OV-3	Homo sapiens	IC50	>	10000	nM	PMID[24593150]
NPT2	Others	Unspecified	n.a.	IC50	=	10000	nM	PMID[24593150]
NPT2	Others	Unspecified	n.a.	IC50	>	10000	nM	PMID[24593150]

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 NPC476850 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	10635
0.1-0.2	38067
0.2-0.3	962
0.3-0.4	137
0.4-0.5	32
0.5-0.6	14
0.6-0.7	4
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	NPC476861
0.8182	Intermediate Similarity	NPC476853
0.7722	Intermediate Similarity	NPC476856
0.7195	Intermediate Similarity	NPC476858
0.6707	Remote Similarity	NPC476857
0.6627	Remote Similarity	NPC23387
0.6429	Remote Similarity	NPC305016
0.6235	Remote Similarity	NPC237155
0.5476	Remote Similarity	NPC476852
0.5476	Remote Similarity	NPC476851
0.5294	Remote Similarity	NPC604270
0.5281	Remote Similarity	NPC263265
0.5227	Remote Similarity	NPC470939
0.5222	Remote Similarity	NPC609366
0.5217	Remote Similarity	NPC117986
0.5213	Remote Similarity	NPC600547
0.5169	Remote Similarity	NPC51568
0.5169	Remote Similarity	NPC234660
0.5165	Remote Similarity	NPC96443
0.5165	Remote Similarity	NPC472653
0.5165	Remote Similarity	NPC290400
0.5158	Remote Similarity	NPC123088

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC476850 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	3651
0.1-0.2	5471
0.2-0.3	28
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