NPASS Compound

Natural Product: NPC474686

Natural Product ID	NPC474686
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	3Beta-Hydroxyrus-18,20(30)-Dien-28-Oic Acid
IUPAC Name	(4aS,6aR,6aR,6bR,8aR,10S,12aR,14aS)-10-hydroxy-1,6a,6b,9,9,12a-hexamethyl-2-methylidene-3,4,5,6,6a,7,8,8a,10,11,12,13,14,14a-tetradecahydropicene-4a-carboxylic acid
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL479472
PubChem CID	10718553
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000012] Lipids and lipid-like molecules [CHEMONTID:0000259] Prenol lipids [CHEMONTID:0001553] Triterpenoids

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 79 83 0 0 0 0 0 0 0 0999 V2000 3.8492 -1.5868 -1.9841 C 0 0 0 0 0 0 0 0 0 0 0 0 4.1737 -0.7624 -0.8371 C 0 0 0 0 0 0 0 0 0 0 0 0 3.2245 -0.0370 -0.2616 C 0 0 0 0 0 0 0 0 0 0 0 0 1.8720 0.0081 -0.6839 C 0 0 0 0 0 0 0 0 0 0 0 0 1.1769 -1.0995 -1.3661 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.3052 -0.9513 -1.6215 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.0122 0.0749 -0.8148 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.4952 0.0116 -0.8337 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.0695 1.4195 -1.0618 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.5408 1.4846 -1.0920 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.1229 0.8663 0.1190 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.5700 -0.4587 0.5229 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.0725 -0.5783 0.4219 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.4956 -0.0418 1.6725 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.1885 0.7057 1.5656 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.3575 0.0472 0.5313 C 0 0 0 0 0 0 0 0 0 0 0 0 0.9869 0.7608 0.2894 C 0 0 0 0 0 0 0 0 0 0 0 0 1.5226 0.9659 1.6650 C 0 0 0 0 0 0 0 0 0 0 0 0 2.8670 1.5693 1.6960 C 0 0 0 0 0 0 0 0 0 0 0 0 3.7843 0.7212 0.8861 C 0 0 0 0 0 0 0 0 0 0 0 0 4.9450 1.5556 0.3566 C 0 0 0 0 0 0 0 0 0 0 0 0 6.0807 0.6273 0.0455 C 0 0 0 0 0 0 0 0 0 0 0 0 5.5724 -0.7175 -0.3104 C 0 0 0 0 0 0 0 0 0 0 0 0 6.2622 -1.8018 -0.2158 C 0 0 0 0 0 0 0 0 0 0 0 0 4.3902 -0.1957 1.8950 C 0 0 0 0 0 0 0 0 0 0 0 0 5.5143 -0.0853 2.3621 O 0 0 0 0 0 0 0 0 0 0 0 0 3.5610 -1.2565 2.3099 O 0 0 0 0 0 0 0 0 0 0 0 0 0.6788 2.1846 -0.2144 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.0551 -1.3322 1.0731 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.3043 -1.5446 -0.2393 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.9988 -0.6347 1.9912 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.0569 1.8035 1.1721 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.9478 -0.7326 -2.0654 C 0 0 0 0 0 0 0 0 0 0 0 0 4.8631 -2.1003 -2.2625 H 0 0 0 0 0 0 0 0 0 0 0 0 3.7259 -1.0652 -2.9456 H 0 0 0 0 0 0 0 0 0 0 0 0 3.3095 -2.5246 -1.8238 H 0 0 0 0 0 0 0 0 0 0 0 0 1.9076 0.7862 -1.5588 H 0 0 0 0 0 0 0 0 0 0 0 0 1.5578 -1.1727 -2.4299 H 0 0 0 0 0 0 0 0 0 0 0 0 1.2746 -2.1099 -0.9825 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.8645 -1.9235 -1.4646 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.5439 -0.7274 -2.6962 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.7369 1.0444 -1.3396 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.6667 2.1600 -0.3818 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.6911 1.6991 -2.0899 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.0192 1.1717 -2.0523 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.7956 2.5893 -1.0401 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.2225 0.7185 -0.0639 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.8874 -1.6932 0.3410 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.1830 0.6712 2.2185 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.3871 -0.8998 2.3877 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.6689 0.5027 2.5579 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.3027 1.7789 1.5466 H 0 0 0 0 0 0 0 0 0 0 0 0 1.4623 0.1292 2.3553 H 0 0 0 0 0 0 0 0 0 0 0 0 0.8491 1.7545 2.1282 H 0 0 0 0 0 0 0 0 0 0 0 0 3.1613 1.6134 2.7889 H 0 0 0 0 0 0 0 0 0 0 0 0 2.9699 2.6102 1.3688 H 0 0 0 0 0 0 0 0 0 0 0 0 5.2667 2.1949 1.2174 H 0 0 0 0 0 0 0 0 0 0 0 0 4.6474 2.2066 -0.4733 H 0 0 0 0 0 0 0 0 0 0 0 0 6.9088 0.6295 0.7728 H 0 0 0 0 0 0 0 0 0 0 0 0 6.5760 1.0939 -0.8840 H 0 0 0 0 0 0 0 0 0 0 0 0 5.8563 -2.7560 -0.5093 H 0 0 0 0 0 0 0 0 0 0 0 0 7.2679 -1.8031 0.1570 H 0 0 0 0 0 0 0 0 0 0 0 0 3.9552 -2.0905 2.7192 H 0 0 0 0 0 0 0 0 0 0 0 0 0.9531 2.1687 -1.3120 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.3260 2.5169 -0.0346 H 0 0 0 0 0 0 0 0 0 0 0 0 1.3553 2.9388 0.2157 H 0 0 0 0 0 0 0 0 0 0 0 0 1.0341 -1.5014 1.2643 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.4563 -1.4816 2.1282 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.5507 -2.1523 0.5267 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.0170 -1.0873 -0.9896 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.0094 -2.1347 0.4218 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.6472 -2.2987 -0.6777 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.0311 -1.1045 2.0179 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.1679 0.3544 2.4818 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.3641 -1.3210 2.5419 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.9104 2.2195 1.3667 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.4890 -0.1975 -2.9503 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.7796 -1.7977 -2.0821 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.0529 -0.5990 -2.2615 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 2 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 1 0 19 20 1 0 20 21 1 0 21 22 1 0 22 23 1 0 23 24 2 0 20 25 1 0 25 26 2 0 25 27 1 0 17 28 1 0 16 29 1 0 12 30 1 0 12 31 1 0 11 32 1 0 8 33 1 0 23 2 1 0 20 3 1 0 17 4 1 0 16 7 1 0 13 8 1 0 1 34 1 0 1 35 1 0 1 36 1 0 4 37 1 0 5 38 1 0 5 39 1 0 6 40 1 0 6 41 1 0 7 42 1 0 9 43 1 0 9 44 1 0 10 45 1 0 10 46 1 0 11 47 1 0 13 48 1 0 14 49 1 0 14 50 1 0 15 51 1 0 15 52 1 0 18 53 1 0 18 54 1 0 19 55 1 0 19 56 1 0 21 57 1 0 21 58 1 0 22 59 1 0 22 60 1 0 24 61 1 0 24 62 1 0 27 63 1 0 28 64 1 0 28 65 1 0 28 66 1 0 29 67 1 0 29 68 1 0 29 69 1 0 30 70 1 0 30 71 1 0 30 72 1 0 31 73 1 0 31 74 1 0 31 75 1 0 32 76 1 0 33 77 1 0 33 78 1 0 33 79 1 0 M END

Standard InCHIKey	DZVARQVBYAEZFI-JZQYXDLISA-N
Standard InCHI	InChI=1S/C30H46O3/c1-18-10-15-30(25(32)33)17-16-28(6)20(24(30)19(18)2)8-9-22-27(5)13-12-23(31)26(3,4)21(27)11-14-29(22,28)7/h20-23,31H,1,8-17H2,2-7H3,(H,32,33)/t20-,21+,22-,23+,27+,28-,29-,30+/m1/s1
SMILES	CC1=C2C3CCC4C5(CCC(C(C5CCC4(C3(CCC2(CCC1=C)C(=O)O)C)C)(C)C)O)C

Calculated Properties

Physi-Chem Properties

Molecular Weight:	454.34	Volume:	503.115 ? Van der Waals volume.
Dense:	0.903	LogP:	3.743 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	3.228 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-4.623 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	1.0	Rigid Bonds:	28.0
TPSA:	57.53 ? Topological Polar Surface Area.	H-Bond Acceptor:	3.0
H-Bond Donor:	2.0	Rings:	5.0
Heavy Atoms:	3.0

MedChem Properties

QED Drug-Likeness Score:	0.442	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	4.84	Fsp³:	0.833
MCE-18:	102.255 ? 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:	0
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.289	Fluc inhibitor:	0.0 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.04 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.077 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.346	Promiscuous compounds:	0.022

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.197	MDCK Permeability:	-4.829
Pgp-inhibitor:	0.0	Pgp-substrate:	0.005
PAMPA:	0.763 ? 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%):	0.001	30% Bioavailability (F30%):	0.002
50% Bioavailability (F50%):	0.783

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.725	MRP1:	1.0
Plasma Protein Binding (PPB):	86.647%	Volume Distribution (VD):	-0.223
Fu:	13.735% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.005
OATP1B3 inhibitor:	0.725	BCRP inhibitor:	0.0
BSEP inhibitor:	0.282

ADMET: Metabolism

CYP1A2-inhibitor:	0.009	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	0.424	CYP2C19-substrate:	0.002
CYP2C9-inhibitor:	0.999	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.334	CYP2D6-substrate:	0.0
CYP3A4-inhibitor:	0.018	CYP3A4-substrate:	0.0
CYP2B6-substrate:	1.0	CYP2C8-inhibitor:	0.001
HLM stability:	0.012 ? 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):

7.864

Half-life (T1/2):

1.154

ADMET: Toxicity

hERG Blockers:	0.062	hERG Blockers (10um):	0.296
Human Hepatotoxicity (H-HT):	0.488	Drug-induced Liver Injury (DILI):	0.14
AMES Toxicity:	0.035	Rat Oral Acute Toxicity:	0.147
Maximum Recommended Daily Dose:	0.749	Skin Sensitization:	0.207
Carcinogencity:	0.348	Eye Corrosion:	0.03
Eye Irritation:	0.591	Respiratory Toxicity:	0.854
Drug-induced Neurotoxicity:	0.231	Ototoxicity:	0.893
Hematotoxicity:	0.156	Drug-induced Nephrotoxicity:	0.124
Genotoxicity:	0.002	RPMI-8226 Immunitoxicity:	0.027
A549 Cytotoxicity:	0.154	Hek293 Cytotoxicity:	0.173
BCF:	1.615 ? 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:	4.566 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.825 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.9 ? 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
NPO928	Baeckea gunniana	Species	Myrtaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[10654412]
NPO928	Baeckea gunniana	Species	Myrtaceae	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	2
Inhibition	2

Activity Type	# Activity
Individual protein	4

Molecular-level activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT2216	Individual protein	DNA polymerase beta	Rattus norvegicus	IC50	=	5600.0	nM	PMID[19581457]
NPT2216	Individual protein	DNA polymerase beta	Rattus norvegicus	IC50	=	2500.0	nM	Open TG-GATES in vivo data: Biochemistry
NPT2216	Individual protein	DNA polymerase beta	Rattus norvegicus	Inhibition	=	82.0	%	Open TG-GATES in vivo data: Biochemistry
NPT2216	Individual protein	DNA polymerase beta	Rattus norvegicus	Inhibition	=	68.0	%	PubChem BioAssay data set

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 NPC474686 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	23046
0.1-0.2	22508
0.2-0.3	3563
0.3-0.4	600
0.4-0.5	129
0.5-0.6	10
0.6-0.7	2
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	Natural Product ID
0.6825	Remote Similarity	NPC181225
0.6719	Remote Similarity	NPC474512
0.5909	Remote Similarity	NPC264317
0.5909	Remote Similarity	NPC294438
0.5652	Remote Similarity	NPC16377
0.5606	Remote Similarity	NPC472608
0.5588	Remote Similarity	NPC476071
0.5507	Remote Similarity	NPC143232
0.5441	Remote Similarity	NPC30583
0.5429	Remote Similarity	NPC18064
0.5238	Remote Similarity	NPC212733
0.5211	Remote Similarity	NPC151191

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC474686 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	6414
0.1-0.2	2664
0.2-0.3	67
0.3-0.4	3
0.4-0.5	1
0.5-0.6	1
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
0.5909	Remote Similarity	NPD7520	Phase 1

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