NPASS Compound

Natural Product: NPC477820

Natural Product ID	NPC477820
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	10,13-dimethyl-17-(6-methylheptan-2-yl)-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthrene-3,12,16-triol
IUPAC Name	10,13-dimethyl-17-(6-methylheptan-2-yl)-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthrene-3,12,16-triol
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	n.a.
PubChem CID	56656818
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000012] Lipids and lipid-like molecules [CHEMONTID:0000258] Steroids and steroid derivatives [CHEMONTID:0003566] Cholestane steroids [CHEMONTID:0001469] Cholesterols and derivatives

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 78 81 0 0 0 0 0 0 0 0999 V2000 6.0454 1.7276 -1.7316 C 0 0 0 0 0 0 0 0 0 0 0 0 6.8119 0.7740 -0.8226 C 0 0 0 0 0 0 0 0 0 0 0 0 8.1255 0.4041 -1.4556 C 0 0 0 0 0 0 0 0 0 0 0 0 5.9613 -0.4558 -0.5383 C 0 0 0 0 0 0 0 0 0 0 0 0 4.6777 -0.0296 0.1437 C 0 0 0 0 0 0 0 0 0 0 0 0 3.8806 -1.2868 0.3993 C 0 0 0 0 0 0 0 0 0 0 0 0 2.5501 -0.9611 1.0925 C 0 0 0 0 0 0 0 0 0 0 0 0 2.8898 -0.3008 2.3663 C 0 0 0 0 0 0 0 0 0 0 0 0 1.6419 -0.3946 0.1283 C 0 0 0 0 0 0 0 0 0 0 0 0 1.3981 -1.4133 -0.9830 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.0975 -1.6124 -1.0697 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.5209 -1.1984 0.3571 C 0 0 0 0 0 0 0 0 0 0 0 0 0.2783 0.0346 0.4951 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.2094 1.0120 -0.5872 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.6592 1.1331 -0.7206 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.5166 0.3016 0.1526 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.9858 -1.0972 0.3683 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.6525 -1.5862 1.6554 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.9802 -0.9505 1.8610 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.7293 -0.5679 0.6399 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.9186 0.0830 -0.4429 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.4443 1.4158 -0.8752 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.9132 1.4077 -1.1825 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.7169 0.7726 -0.0865 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.8002 0.4400 1.0686 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.4723 -0.3105 -0.5056 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.8930 -0.8310 -1.6275 C 0 0 0 0 0 0 0 0 0 0 0 0 0.3477 2.2618 -0.2158 O 0 0 0 0 0 0 0 0 0 0 0 0 0.1417 0.7965 1.7733 C 0 0 0 0 0 0 0 0 0 0 0 0 1.9969 -1.1014 -2.1670 O 0 0 0 0 0 0 0 0 0 0 0 0 5.3793 2.3880 -1.1085 H 0 0 0 0 0 0 0 0 0 0 0 0 5.4018 1.0905 -2.3741 H 0 0 0 0 0 0 0 0 0 0 0 0 6.7053 2.3967 -2.2870 H 0 0 0 0 0 0 0 0 0 0 0 0 7.0306 1.2389 0.1605 H 0 0 0 0 0 0 0 0 0 0 0 0 8.8490 1.2223 -1.1982 H 0 0 0 0 0 0 0 0 0 0 0 0 8.5387 -0.5114 -1.0119 H 0 0 0 0 0 0 0 0 0 0 0 0 8.0594 0.3221 -2.5600 H 0 0 0 0 0 0 0 0 0 0 0 0 5.7581 -1.0203 -1.4814 H 0 0 0 0 0 0 0 0 0 0 0 0 6.5571 -1.0986 0.1483 H 0 0 0 0 0 0 0 0 0 0 0 0 4.9743 0.4926 1.0721 H 0 0 0 0 0 0 0 0 0 0 0 0 4.1654 0.6647 -0.5571 H 0 0 0 0 0 0 0 0 0 0 0 0 3.6201 -1.6883 -0.5971 H 0 0 0 0 0 0 0 0 0 0 0 0 4.4889 -1.9842 0.9735 H 0 0 0 0 0 0 0 0 0 0 0 0 2.1823 -1.9951 1.3981 H 0 0 0 0 0 0 0 0 0 0 0 0 3.7385 -0.9216 2.8074 H 0 0 0 0 0 0 0 0 0 0 0 0 3.3480 0.7031 2.2837 H 0 0 0 0 0 0 0 0 0 0 0 0 2.1188 -0.3590 3.1673 H 0 0 0 0 0 0 0 0 0 0 0 0 2.1241 0.4789 -0.4145 H 0 0 0 0 0 0 0 0 0 0 0 0 1.7797 -2.4392 -0.6892 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.5956 -1.0311 -1.8410 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.4012 -2.6644 -1.1902 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.2012 -2.0410 0.9985 H 0 0 0 0 0 0 0 0 0 0 0 0 0.2551 0.7922 -1.5677 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.9838 2.2076 -0.5723 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.9792 0.9281 -1.7874 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.7663 0.7798 1.1467 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.4056 -1.7926 -0.4203 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.9863 -1.2940 2.4880 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.7448 -2.7022 1.6137 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.9426 -0.0752 2.5748 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.6188 -1.7023 2.4150 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.2584 -1.4885 0.2618 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.9221 1.6660 -1.8453 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.2016 2.2434 -0.1921 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.2026 2.4854 -1.3597 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.1567 0.9018 -2.1504 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.4140 1.5643 0.3032 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.3513 0.0644 1.9533 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.2613 1.3795 1.3229 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.2621 -0.3651 0.1223 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.9566 -0.8205 -2.1989 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.6906 -0.4999 -2.3565 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.2187 -1.8765 -1.3488 H 0 0 0 0 0 0 0 0 0 0 0 0 0.3725 2.8746 -0.9927 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.1392 0.2229 2.6478 H 0 0 0 0 0 0 0 0 0 0 0 0 1.0985 1.3857 1.8855 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.6144 1.6393 1.7090 H 0 0 0 0 0 0 0 0 0 0 0 0 2.4921 -0.2286 -2.1483 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 1 0 2 4 1 0 4 5 1 0 5 6 1 0 6 7 1 0 7 8 1 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 1 0 20 21 1 0 21 22 1 0 22 23 1 0 23 24 1 0 24 25 1 0 24 26 1 0 21 27 1 0 14 28 1 0 13 29 1 0 10 30 1 0 13 9 1 0 17 12 1 0 21 16 1 0 25 20 1 0 1 31 1 0 1 32 1 0 1 33 1 0 2 34 1 0 3 35 1 0 3 36 1 0 3 37 1 0 4 38 1 0 4 39 1 0 5 40 1 0 5 41 1 0 6 42 1 0 6 43 1 0 7 44 1 0 8 45 1 0 8 46 1 0 8 47 1 0 9 48 1 0 10 49 1 0 11 50 1 0 11 51 1 0 12 52 1 0 14 53 1 0 15 54 1 0 15 55 1 0 16 56 1 0 17 57 1 0 18 58 1 0 18 59 1 0 19 60 1 0 19 61 1 0 20 62 1 0 22 63 1 0 22 64 1 0 23 65 1 0 23 66 1 0 24 67 1 0 25 68 1 0 25 69 1 0 26 70 1 0 27 71 1 0 27 72 1 0 27 73 1 0 28 74 1 0 29 75 1 0 29 76 1 0 29 77 1 0 30 78 1 0 M END

Standard InCHIKey	UYOSSIFSBNNKRC-UHFFFAOYSA-N
Standard InCHI	InChI=1S/C27H48O3/c1-16(2)7-6-8-17(3)25-23(29)14-22-20-10-9-18-13-19(28)11-12-26(18,4)21(20)15-24(30)27(22,25)5/h16-25,28-30H,6-15H2,1-5H3
SMILES	CC(C)CCCC(C)C1C(CC2C1(C(CC3C2CCC4C3(CCC(C4)O)C)O)C)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	420.36	Volume:	467.693 ? Van der Waals volume.
Dense:	0.899	LogP:	5.011 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	4.546 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-5.547 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	5.0	Rigid Bonds:	20.0
TPSA:	60.69 ? Topological Polar Surface Area.	H-Bond Acceptor:	3.0
H-Bond Donor:	3.0	Rings:	4.0
Heavy Atoms:	3.0

MedChem Properties

QED Drug-Likeness Score:	0.557	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	4.697	Fsp³:	1.0
MCE-18:	73.63 ? 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:	0.386	Fluc inhibitor:	0.0 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.011 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.003 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.281	Promiscuous compounds:	0.036

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.212	MDCK Permeability:	-4.893
Pgp-inhibitor:	0.0	Pgp-substrate:	0.368
PAMPA:	0.988 ? 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):	0.025
20% Bioavailability (F20%):	0.085	30% Bioavailability (F30%):	0.669
50% Bioavailability (F50%):	0.999

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.614	MRP1:	0.992
Plasma Protein Binding (PPB):	62.234%	Volume Distribution (VD):	0.095
Fu:	34.095% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.001
OATP1B3 inhibitor:	0.427	BCRP inhibitor:	0.015
BSEP inhibitor:	0.0

ADMET: Metabolism

CYP1A2-inhibitor:	0.0	CYP1A2-substrate:	0.002
CYP2C19-inhibitor:	0.955	CYP2C19-substrate:	0.313
CYP2C9-inhibitor:	0.932	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.282	CYP2D6-substrate:	0.001
CYP3A4-inhibitor:	0.971	CYP3A4-substrate:	0.398
CYP2B6-substrate:	0.999	CYP2C8-inhibitor:	0.998
HLM stability:	0.174 ? 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):

19.363

Half-life (T1/2):

2.277

ADMET: Toxicity

hERG Blockers:	0.214	hERG Blockers (10um):	0.713
Human Hepatotoxicity (H-HT):	0.587	Drug-induced Liver Injury (DILI):	0.022
AMES Toxicity:	0.136	Rat Oral Acute Toxicity:	0.069
Maximum Recommended Daily Dose:	0.703	Skin Sensitization:	0.05
Carcinogencity:	0.276	Eye Corrosion:	0.007
Eye Irritation:	0.423	Respiratory Toxicity:	0.623
Drug-induced Neurotoxicity:	0.115	Ototoxicity:	0.949
Hematotoxicity:	0.043	Drug-induced Nephrotoxicity:	0.116
Genotoxicity:	0.0	RPMI-8226 Immunitoxicity:	0.032
A549 Cytotoxicity:	0.192	Hek293 Cytotoxicity:	0.226
BCF:	1.946 ? 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:	4.22 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.547 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.864 ? 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
NPO33580	Psammoclema sp.	Species	Chondropsidae	Eukaryota	n.a.	Nelson Bay, New South Wales, Australia (3243'0.5'' S, 15208'25.0'' E)	2006-OCT	PMID[19132863]
NPO33580	Psammoclema sp.	Species	Chondropsidae	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
GI50	4

Activity Type	# Activity
Cell line	4

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
NPT139	Cell line	HT-29	Homo sapiens	GI50	=	5000	nM	PMID[19132863]
NPT83	Cell line	MCF7	Homo sapiens	GI50	=	5500	nM	PMID[19132863]
NPT179	Cell line	A2780	Homo sapiens	GI50	=	5400	nM	PMID[19132863]
NPT90	Cell line	DU-145	Homo sapiens	GI50	=	6700	nM	PMID[19132863]

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 NPC477820 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	33343
0.1-0.2	15453
0.2-0.3	917
0.3-0.4	109
0.4-0.5	25
0.5-0.6	6
0.6-0.7	3
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
0.75	Intermediate Similarity	NPC477819
0.75	Intermediate Similarity	NPC477817
0.6429	Remote Similarity	NPC477818
0.6275	Remote Similarity	NPC71460
0.6275	Remote Similarity	NPC218585
0.5424	Remote Similarity	NPC4209
0.5192	Remote Similarity	NPC114891
0.5094	Remote Similarity	NPC281540
0.5094	Remote Similarity	NPC159654
0.5094	Remote Similarity	NPC167995
0.5094	Remote Similarity	NPC118937

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC477820 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	8319
0.1-0.2	753
0.2-0.3	57
0.3-0.4	12
0.4-0.5	8
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
0.5424	Remote Similarity	NPD6117	Phase 4

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