NPASS Compound

Natural Product: NPC473473

Natural Product ID	NPC473473
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	SHMUHJHCJILCGR-RDZAXEFUSA-N
IUPAC Name	n.a.
Synonyms	11Beta-Acetoxygedunin
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL442681
PubChem CID	44559131
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 75 80 0 0 0 0 0 0 0 0999 V2000 1.1181 -4.0910 3.7117 C 0 0 0 0 0 0 0 0 0 0 0 0 1.1270 -3.4623 2.3514 C 0 0 0 0 0 0 0 0 0 0 0 0 1.1279 -4.1625 1.3334 O 0 0 0 0 0 0 0 0 0 0 0 0 1.1343 -2.0975 2.1974 O 0 0 0 0 0 0 0 0 0 0 0 0 1.1372 -1.3701 1.0208 C 0 0 0 0 0 0 0 0 0 0 0 0 2.5142 -0.7348 0.7911 C 0 0 0 0 0 0 0 0 0 0 0 0 2.6112 -0.4107 -0.6556 C 0 0 0 0 0 0 0 0 0 0 0 0 3.9837 -0.1106 -1.1447 C 0 0 0 0 0 0 0 0 0 0 0 0 3.9829 0.8026 -2.3172 C 0 0 0 0 0 0 0 0 0 0 0 0 4.9892 1.4462 -2.6100 O 0 0 0 0 0 0 0 0 0 0 0 0 2.7150 0.8652 -3.0705 C 0 0 0 0 0 0 0 0 0 0 0 0 1.5652 0.8115 -2.4081 C 0 0 0 0 0 0 0 0 0 0 0 0 1.5876 0.6921 -0.9206 C 0 0 0 0 0 0 0 0 0 0 0 0 0.2282 0.3023 -0.4770 C 0 0 0 0 0 0 0 0 0 0 0 0 0.0480 -0.3366 0.8609 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.3227 -0.9965 0.8385 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.7622 -1.8892 1.8675 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.2822 -2.4201 0.6994 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.2439 -2.0243 2.0005 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.8180 -2.4064 3.0529 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.0968 -1.7217 0.9223 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.4678 -1.2363 -0.2278 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.4285 -0.2217 0.2540 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.0991 0.5857 -0.9696 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.7923 1.3352 -0.8204 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.8895 2.4361 0.0179 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.7673 3.7405 -0.3603 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.5479 4.0122 -1.5724 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.8849 4.8794 0.6199 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.1719 0.6935 1.1962 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.4223 -0.5910 -1.1618 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.4432 0.2939 -0.9018 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.0279 0.6061 -2.0191 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.4933 0.0057 -3.0467 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.4708 -0.7648 -2.5531 C 0 0 0 0 0 0 0 0 0 0 0 0 0.0939 0.5178 2.0669 C 0 0 0 0 0 0 0 0 0 0 0 0 2.0559 2.0161 -0.3830 C 0 0 0 0 0 0 0 0 0 0 0 0 4.9740 0.3828 -0.1603 C 0 0 0 0 0 0 0 0 0 0 0 0 4.5483 -1.4385 -1.6886 C 0 0 0 0 0 0 0 0 0 0 0 0 0.5016 -3.5020 4.4224 H 0 0 0 0 0 0 0 0 0 0 0 0 2.1656 -4.1508 4.0370 H 0 0 0 0 0 0 0 0 0 0 0 0 0.6984 -5.0963 3.5965 H 0 0 0 0 0 0 0 0 0 0 0 0 1.0475 -2.0859 0.1647 H 0 0 0 0 0 0 0 0 0 0 0 0 3.2591 -1.5020 1.0373 H 0 0 0 0 0 0 0 0 0 0 0 0 2.5595 0.1805 1.3609 H 0 0 0 0 0 0 0 0 0 0 0 0 2.1983 -1.2982 -1.2198 H 0 0 0 0 0 0 0 0 0 0 0 0 2.7428 0.9589 -4.1463 H 0 0 0 0 0 0 0 0 0 0 0 0 0.6875 0.8519 -3.0248 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.0169 -0.5673 -1.1846 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.2736 -2.0319 2.8503 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.9183 -2.0321 -0.7864 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.9197 1.3052 -1.1579 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.0170 -0.0451 -1.8765 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.5710 1.7362 -1.8275 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.9091 5.2614 0.6814 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.4678 4.5386 1.5796 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.2054 5.6783 0.2471 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.5854 1.5875 0.6378 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.0395 0.2512 1.6865 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.5457 1.1389 1.9840 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.7297 0.6787 0.0591 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.8293 0.1278 -4.0608 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.8099 -1.3994 -3.1233 H 0 0 0 0 0 0 0 0 0 0 0 0 1.0700 0.5003 2.6369 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.5973 0.0536 2.8379 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.1877 1.5510 2.0025 H 0 0 0 0 0 0 0 0 0 0 0 0 1.8628 2.8086 -1.1295 H 0 0 0 0 0 0 0 0 0 0 0 0 3.1393 2.0111 -0.2183 H 0 0 0 0 0 0 0 0 0 0 0 0 1.5684 2.3113 0.5631 H 0 0 0 0 0 0 0 0 0 0 0 0 4.6105 0.4863 0.8806 H 0 0 0 0 0 0 0 0 0 0 0 0 5.8849 -0.2827 -0.0549 H 0 0 0 0 0 0 0 0 0 0 0 0 5.4327 1.3783 -0.4133 H 0 0 0 0 0 0 0 0 0 0 0 0 3.7312 -2.1304 -1.9523 H 0 0 0 0 0 0 0 0 0 0 0 0 5.2161 -1.2654 -2.5352 H 0 0 0 0 0 0 0 0 0 0 0 0 5.1377 -1.9445 -0.8885 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 2 0 9 11 1 0 11 12 2 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 17 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 1 0 25 26 1 0 26 27 1 0 27 28 2 0 27 29 1 0 23 30 1 0 22 31 1 0 31 32 2 0 32 33 1 0 33 34 1 0 34 35 2 0 15 36 1 0 13 37 1 0 8 38 1 0 8 39 1 0 15 5 1 0 13 7 1 0 25 14 1 0 18 16 1 0 23 16 1 0 35 31 1 0 1 40 1 0 1 41 1 0 1 42 1 0 5 43 1 0 6 44 1 0 6 45 1 0 7 46 1 0 11 47 1 0 12 48 1 0 14 49 1 0 17 50 1 0 22 51 1 0 24 52 1 0 24 53 1 0 25 54 1 0 29 55 1 0 29 56 1 0 29 57 1 0 30 58 1 0 30 59 1 0 30 60 1 0 32 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 39 73 1 0 39 74 1 0 39 75 1 0 M END

Standard InCHIKey	SHMUHJHCJILCGR-RDZAXEFUSA-N
Standard InCHI	InChI=1S/C30H36O9/c1-15(31)36-18-13-28(6)23(17-9-11-35-14-17)38-25(34)24-30(28,39-24)29(7)21(37-16(2)32)12-19-26(3,4)20(33)8-10-27(19,5)22(18)29/h8-11,14,18-19,21-24H,12-13H2,1-7H3/t18-,19-,21+,22+,23-,24+,27-,28-,29+,30+/m0/s1
SMILES	CC(=O)OC1CC2C(C(=O)C=CC2(C3C1(C45C(O4)C(=O)OC(C5(CC3OC(=O)C)C)C6=COC=C6)C)C)(C)C

Calculated Properties

Physi-Chem Properties

Molecular Weight:	540.24	Volume:	536.754 ? Van der Waals volume.
Dense:	1.006	LogP:	1.877 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	2.165 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-4.093 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	5.0	Rigid Bonds:	32.0
TPSA:	121.64 ? Topological Polar Surface Area.	H-Bond Acceptor:	9.0
H-Bond Donor:	0.0	Rings:	6.0
Heavy Atoms:	9.0

MedChem Properties

QED Drug-Likeness Score:	0.317	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	5.796	Fsp³:	0.667
MCE-18:	198.88 ? 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:	0.046	Fluc inhibitor:	0.0 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.006 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.247 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.205	Promiscuous compounds:	0.004

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-4.939	MDCK Permeability:	-4.581
Pgp-inhibitor:	0.028	Pgp-substrate:	0.195
PAMPA:	0.913 ? 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):	0.004
20% Bioavailability (F20%):	0.008	30% Bioavailability (F30%):	0.03
50% Bioavailability (F50%):	0.78

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.052	MRP1:	1.0
Plasma Protein Binding (PPB):	88.125%	Volume Distribution (VD):	-0.087
Fu:	13.457% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.007
OATP1B3 inhibitor:	0.647	BCRP inhibitor:	0.001
BSEP inhibitor:	0.912

ADMET: Metabolism

CYP1A2-inhibitor:	0.011	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	0.999	CYP2C19-substrate:	0.0
CYP2C9-inhibitor:	0.026	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.124
CYP3A4-inhibitor:	0.997	CYP3A4-substrate:	0.0
CYP2B6-substrate:	1.0	CYP2C8-inhibitor:	0.816
HLM stability:	0.958 ? 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):

2.561

Half-life (T1/2):

1.015

ADMET: Toxicity

hERG Blockers:	0.04	hERG Blockers (10um):	0.249
Human Hepatotoxicity (H-HT):	0.272	Drug-induced Liver Injury (DILI):	0.882
AMES Toxicity:	0.325	Rat Oral Acute Toxicity:	0.549
Maximum Recommended Daily Dose:	0.871	Skin Sensitization:	0.336
Carcinogencity:	0.611	Eye Corrosion:	0.001
Eye Irritation:	0.3	Respiratory Toxicity:	0.201
Drug-induced Neurotoxicity:	0.217	Ototoxicity:	0.56
Hematotoxicity:	0.103	Drug-induced Nephrotoxicity:	0.135
Genotoxicity:	0.96	RPMI-8226 Immunitoxicity:	0.049
A549 Cytotoxicity:	0.063	Hek293 Cytotoxicity:	0.221
BCF:	0.65 ? 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:	3.536 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.673 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.988 ? 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
NPO29947	Cedrela sinensis	Species	Meliaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[16989525]
NPO29947	Cedrela sinensis	Species	Meliaceae	Eukaryota	n.a.	cortex	n.a.	PMID[16989525]
NPO29947	Cedrela sinensis	Species	Meliaceae	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

Activity Type	# Activity
IC50	1

Activity Type	# Activity
Cell line	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
NPT168	Cell line	P388	Mus musculus	IC50	=	3.8	ug.mL-1	PMID[3373220]

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 NPC473473 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	15414
0.1-0.2	32794
0.2-0.3	1452
0.3-0.4	131
0.4-0.5	40
0.5-0.6	12
0.6-0.7	8
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	NPC475295
0.7662	Intermediate Similarity	NPC209364
0.7662	Intermediate Similarity	NPC286722
0.7662	Intermediate Similarity	NPC605015
0.7468	Intermediate Similarity	NPC96443
0.7468	Intermediate Similarity	NPC290400
0.6951	Remote Similarity	NPC611267
0.631	Remote Similarity	NPC609366
0.631	Remote Similarity	NPC611370
0.625	Remote Similarity	NPC302392
0.6235	Remote Similarity	NPC473766
0.6098	Remote Similarity	NPC60973
0.6098	Remote Similarity	NPC605384
0.6092	Remote Similarity	NPC473753
0.5882	Remote Similarity	NPC51568
0.5882	Remote Similarity	NPC234660
0.5882	Remote Similarity	NPC5079
0.5833	Remote Similarity	NPC107646
0.5568	Remote Similarity	NPC475381
0.5529	Remote Similarity	NPC602263
0.5506	Remote Similarity	NPC126723
0.5506	Remote Similarity	NPC476860
0.5402	Remote Similarity	NPC134254
0.5402	Remote Similarity	NPC335761
0.5341	Remote Similarity	NPC302369
0.5053	Remote Similarity	NPC600547

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC473473 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	4269
0.1-0.2	4860
0.2-0.3	21
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