NPASS Compound

Natural Product: NPC476853

Natural Product ID	NPC476853
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	[(1R,2R,4S,7S,8S,10S,11R,12R,13S,18R)-7-(furan-3-yl)-10-hydroxy-1,8,12,17,17-pentamethyl-5,15,20-trioxo-3,6,16-trioxapentacyclo[9.9.0.02,4.02,8.012,18]icosan-13-yl] acetate
IUPAC Name	[(1R,2R,4S,7S,8S,10S,11R,12R,13S,18R)-7-(furan-3-yl)-10-hydroxy-1,8,12,17,17-pentamethyl-5,15,20-trioxo-3,6,16-trioxapentacyclo[9.9.0.02,4.02,8.012,18]icosan-13-yl] acetate
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	n.a.
PubChem CID	90670770
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000012] Lipids and lipid-like molecules [CHEMONTID:0000259] Prenol lipids [CHEMONTID:0001553] Triterpenoids [CHEMONTID:0002380] Limonoids

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 72 77 0 0 0 0 0 0 0 0999 V2000 -3.7740 -3.8008 0.9399 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.6905 -2.2993 0.9446 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.7540 -1.6300 0.8968 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.5087 -1.6197 0.9986 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.3164 -0.2358 1.0059 C 0 0 1 0 0 0 0 0 0 0 0 0 -1.8084 0.3166 2.3012 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.4521 1.6343 2.5502 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.3094 2.0446 3.7264 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.1626 2.4227 1.6580 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.8824 2.5320 0.2518 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.6738 1.8248 -0.1783 C 0 0 1 0 0 0 0 0 0 0 0 0 -1.6477 0.3238 -0.2293 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.1814 -0.0372 -0.2644 C 0 0 1 0 0 0 0 0 0 0 0 0 0.1824 -1.4110 0.1711 C 0 0 2 0 0 0 0 0 0 0 0 0 1.6528 -1.5778 0.3345 C 0 0 0 0 0 0 0 0 0 0 0 0 2.5351 -0.4709 -0.1000 C 0 0 1 0 0 0 0 0 0 0 0 0 3.8803 -1.1162 -0.4230 C 0 0 1 0 0 0 0 0 0 0 0 0 4.8457 -0.1511 -0.7423 O 0 0 0 0 0 0 0 0 0 0 0 0 4.4066 0.9719 -1.4682 C 0 0 0 0 0 0 0 0 0 0 0 0 5.2063 1.9271 -1.5693 O 0 0 0 0 0 0 0 0 0 0 0 0 3.0443 0.9162 -2.0414 C 0 0 2 0 0 0 0 0 0 0 0 0 2.0434 0.2547 -1.3210 C 0 0 2 0 0 0 0 0 0 0 0 0 0.5798 0.4599 -1.4320 C 0 0 2 0 0 0 0 0 0 0 0 0 0.3555 1.9591 -1.4608 C 0 0 0 0 0 0 0 0 0 0 0 0 1.2723 2.7585 -1.4870 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.0877 2.4054 -1.4549 C 0 0 0 0 0 0 0 0 0 0 0 0 0.1093 -0.0391 -2.7765 C 0 0 0 0 0 0 0 0 0 0 0 0 2.6813 -0.3469 -2.5367 O 0 0 0 0 0 0 0 0 0 0 0 0 4.3915 -1.9513 0.6954 C 0 0 0 0 0 0 0 0 0 0 0 0 4.2743 -3.3434 0.7871 C 0 0 0 0 0 0 0 0 0 0 0 0 4.8454 -3.7021 1.8934 O 0 0 0 0 0 0 0 0 0 0 0 0 5.3298 -2.7042 2.5483 C 0 0 0 0 0 0 0 0 0 0 0 0 5.0668 -1.5628 1.8261 C 0 0 0 0 0 0 0 0 0 0 0 0 2.8385 0.5724 0.9655 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.4117 -2.4236 -0.5957 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.4655 -0.2462 -1.3508 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.1133 2.3754 -0.5787 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.5377 4.0395 0.1290 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.4444 -4.0694 0.0972 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.7795 -4.2257 0.7008 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.1253 -4.1918 1.9058 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.3797 0.1650 0.9335 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.7382 0.4475 2.3953 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.1055 -0.4219 3.0965 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.8884 2.0937 0.6037 H 0 0 0 0 0 0 0 0 0 0 0 0 0.2100 0.5859 0.6101 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.2273 -1.5758 1.2148 H 0 0 0 0 0 0 0 0 0 0 0 0 1.9197 -2.5026 -0.2639 H 0 0 0 0 0 0 0 0 0 0 0 0 1.9813 -1.8633 1.3751 H 0 0 0 0 0 0 0 0 0 0 0 0 3.6917 -1.8026 -1.3013 H 0 0 0 0 0 0 0 0 0 0 0 0 2.8772 1.7053 -2.8103 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.0672 3.5047 -1.3712 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.6173 2.1211 -2.3594 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.3766 0.7633 -3.3959 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.4293 -0.9864 -2.7548 H 0 0 0 0 0 0 0 0 0 0 0 0 1.0077 -0.2772 -3.4330 H 0 0 0 0 0 0 0 0 0 0 0 0 3.7827 -3.9664 0.0371 H 0 0 0 0 0 0 0 0 0 0 0 0 5.8650 -2.6783 3.5062 H 0 0 0 0 0 0 0 0 0 0 0 0 5.3463 -0.5349 2.0970 H 0 0 0 0 0 0 0 0 0 0 0 0 3.9238 0.8913 0.9267 H 0 0 0 0 0 0 0 0 0 0 0 0 2.6771 0.2184 1.9931 H 0 0 0 0 0 0 0 0 0 0 0 0 2.3286 1.5583 0.7447 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.0047 -3.2730 -0.3450 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.4154 0.2540 -2.3037 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.3302 -1.3472 -1.3600 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.5527 -0.1405 -1.0431 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.7837 2.1659 -1.6257 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.6949 3.3441 -0.6865 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.8604 1.6700 -0.1917 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.2153 4.6301 0.8162 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.8113 4.4147 -0.8814 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.5278 4.2536 0.4599 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 2 0 7 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 1 0 19 20 2 0 19 21 1 0 21 22 1 0 22 23 1 0 23 24 1 0 24 25 2 0 24 26 1 0 23 27 1 6 22 28 1 6 17 29 1 0 29 30 2 0 30 31 1 0 31 32 1 0 32 33 2 0 16 34 1 1 14 35 1 0 12 36 1 6 10 37 1 0 10 38 1 0 12 5 1 0 26 11 1 0 23 13 1 0 22 16 1 0 28 21 1 0 33 29 1 0 1 39 1 0 1 40 1 0 1 41 1 0 5 42 1 6 6 43 1 0 6 44 1 0 11 45 1 1 13 46 1 1 14 47 1 1 15 48 1 0 15 49 1 0 17 50 1 6 21 51 1 6 26 52 1 0 26 53 1 0 27 54 1 0 27 55 1 0 27 56 1 0 30 57 1 0 32 58 1 0 33 59 1 0 34 60 1 0 34 61 1 0 34 62 1 0 35 63 1 0 36 64 1 0 36 65 1 0 36 66 1 0 37 67 1 0 37 68 1 0 37 69 1 0 38 70 1 0 38 71 1 0 38 72 1 0 M END

Standard InCHIKey	XJLFQSIGXGHTAE-LIAMLSCRSA-N
Standard InCHI	InChI=1S/C28H34O10/c1-13(29)35-18-10-19(32)37-24(2,3)16-9-17(31)27(6)20(26(16,18)5)15(30)11-25(4)21(14-7-8-34-12-14)36-23(33)22-28(25,27)38-22/h7-8,12,15-16,18,20-22,30H,9-11H2,1-6H3/t15-,16-,18-,20+,21-,22+,25-,26+,27+,28+/m0/s1
SMILES	CC(=O)O[C@H]1CC(=O)OC([C@H]2[C@]1([C@H]3[C@H](C[C@]4([C@@H](OC(=O)[C@@H]5[C@@]4([C@@]3(C(=O)C2)C)O5)C6=COC=C6)C)O)C)(C)C

Calculated Properties

Physi-Chem Properties

Molecular Weight:	530.22	Volume:	513.589 ? Van der Waals volume.
Dense:	1.032	LogP:	1.124 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	1.388 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-3.274 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	3.0	Rigid Bonds:	33.0
TPSA:	141.87 ? Topological Polar Surface Area.	H-Bond Acceptor:	10.0
H-Bond Donor:	1.0	Rings:	6.0
Heavy Atoms:	10.0

MedChem Properties

QED Drug-Likeness Score:	0.344	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	5.868	Fsp³:	0.714
MCE-18:	201.667 ? 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:	0.564	Fluc inhibitor:	0.003 ? 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:	0.048	Promiscuous compounds:	0.409

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.372	MDCK Permeability:	-5.002
Pgp-inhibitor:	0.979	Pgp-substrate:	0.365
PAMPA:	0.817 ? 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):	0.008
20% Bioavailability (F20%):	0.081	30% Bioavailability (F30%):	0.443
50% Bioavailability (F50%):	0.753

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.007	MRP1:	0.99
Plasma Protein Binding (PPB):	78.626%	Volume Distribution (VD):	-0.44
Fu:	20.74% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.999
OATP1B3 inhibitor:	0.988	BCRP inhibitor:	0.076
BSEP inhibitor:	0.989

ADMET: Metabolism

CYP1A2-inhibitor:	0.011	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	0.281	CYP2C19-substrate:	0.001
CYP2C9-inhibitor:	0.003	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.007
CYP3A4-inhibitor:	0.215	CYP3A4-substrate:	0.0
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.14
HLM stability:	0.286 ? 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):

6.293

Half-life (T1/2):

1.439

ADMET: Toxicity

hERG Blockers:	0.014	hERG Blockers (10um):	0.147
Human Hepatotoxicity (H-HT):	0.475	Drug-induced Liver Injury (DILI):	0.896
AMES Toxicity:	0.461	Rat Oral Acute Toxicity:	0.801
Maximum Recommended Daily Dose:	0.948	Skin Sensitization:	0.985
Carcinogencity:	0.489	Eye Corrosion:	0.011
Eye Irritation:	0.855	Respiratory Toxicity:	0.852
Drug-induced Neurotoxicity:	0.124	Ototoxicity:	0.763
Hematotoxicity:	0.455	Drug-induced Nephrotoxicity:	0.959
Genotoxicity:	0.983	RPMI-8226 Immunitoxicity:	0.217
A549 Cytotoxicity:	0.011	Hek293 Cytotoxicity:	0.014
BCF:	0.493 ? 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:	3.158 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.895 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.404 ? 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	5

Activity Type	# Activity
Cell line	4
Others	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
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]

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 NPC476853 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	11608
0.1-0.2	36604
0.2-0.3	1443
0.3-0.4	146
0.4-0.5	30
0.5-0.6	18
0.6-0.7	3
0.7-0.8	0
0.8-0.85	2
0.85-0.9	0
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Natural Product ID
0.8182	Intermediate Similarity	NPC476861
0.8182	Intermediate Similarity	NPC476850
0.775	Intermediate Similarity	NPC476856
0.7722	Intermediate Similarity	NPC237155
0.7654	Intermediate Similarity	NPC476858
0.6867	Remote Similarity	NPC23387
0.6163	Remote Similarity	NPC476857
0.6163	Remote Similarity	NPC611370
0.5909	Remote Similarity	NPC305016
0.5814	Remote Similarity	NPC470939
0.5647	Remote Similarity	NPC476854
0.5647	Remote Similarity	NPC476855
0.5556	Remote Similarity	NPC96443
0.5556	Remote Similarity	NPC290400
0.5506	Remote Similarity	NPC263265
0.5312	Remote Similarity	NPC472651
0.5275	Remote Similarity	NPC609366
0.5217	Remote Similarity	NPC472653
0.5172	Remote Similarity	NPC604270
0.5104	Remote Similarity	NPC600547
0.51	Remote Similarity	NPC472652
0.5056	Remote Similarity	NPC60973
0.5056	Remote Similarity	NPC605384
0.5055	Remote Similarity	NPC51568
0.5055	Remote Similarity	NPC234660
0.5052	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 NPC476853 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	3836
0.1-0.2	5281
0.2-0.3	33
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