NPASS Compound

Natural Product: NPC474512

Natural Product ID	NPC474512
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	Acridocarpusic Acid D
IUPAC Name	(2R,4aS,6aR,6aR,6bR,8aR,10R,12aR,14aS)-10-hydroxy-2,6a,6b,9,9,12a-hexamethyl-3,4,5,6,6a,7,8,8a,10,11,12,13,14,14a-tetradecahydro-2H-picene-4a-carboxylic acid
Synonyms	Acridocarpusic Acid D
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL470463
PubChem CID	44559546
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0004603] Organic oxygen compounds [CHEMONTID:0000323] Organooxygen compounds [CHEMONTID:0000129] Alcohols and polyols [CHEMONTID:0001292] Cyclic alcohols 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 82 0 0 0 0 0 0 0 0999 V2000 4.9191 -2.4838 -1.3278 C 0 0 0 0 0 0 0 0 0 0 0 0 4.9372 -1.0192 -1.7788 C 0 0 2 0 0 0 0 0 0 0 0 0 5.8739 -0.2899 -0.8776 C 0 0 0 0 0 0 0 0 0 0 0 0 5.2933 -0.2509 0.5035 C 0 0 0 0 0 0 0 0 0 0 0 0 4.0127 0.5409 0.5746 C 0 0 1 0 0 0 0 0 0 0 0 0 3.1595 0.2854 -0.6407 C 0 0 0 0 0 0 0 0 0 0 0 0 3.5925 -0.4103 -1.6735 C 0 0 0 0 0 0 0 0 0 0 0 0 1.7926 0.8876 -0.5504 C 0 0 1 0 0 0 0 0 0 0 0 0 1.0557 0.8613 -1.8287 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.3482 1.4227 -1.5484 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.9867 0.4220 -0.6254 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.3569 0.5416 0.7149 C 0 0 1 0 0 0 0 0 0 0 0 0 1.1068 0.2258 0.6093 C 0 0 2 0 0 0 0 0 0 0 0 0 1.8627 0.6904 1.8536 C 0 0 0 0 0 0 0 0 0 0 0 0 3.2864 0.1758 1.8330 C 0 0 0 0 0 0 0 0 0 0 0 0 1.3234 -1.2849 0.5531 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.5237 1.8701 1.3768 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.9631 -0.5019 1.6499 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.4795 -0.3023 1.7484 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.9995 -0.5546 0.3411 C 0 0 2 0 0 0 0 0 0 0 0 0 -2.4858 0.4487 -0.6528 C 0 0 1 0 0 0 0 0 0 0 0 0 -3.0629 1.8088 -0.5548 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.9203 -0.1265 -2.0134 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.4034 -0.1703 -2.1477 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.1712 -0.2262 -0.8853 C 0 0 2 0 0 0 0 0 0 0 0 0 -4.4573 -0.8218 0.2807 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.7381 -2.3344 0.2604 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.1937 -0.3185 1.5308 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.3206 -1.0195 -1.1270 O 0 0 0 0 0 0 0 0 0 0 0 0 4.3599 1.9782 0.5583 C 0 0 0 0 0 0 0 0 0 0 0 0 4.0300 2.6872 1.5358 O 0 0 0 0 0 0 0 0 0 0 0 0 5.0330 2.5782 -0.4875 O 0 0 0 0 0 0 0 0 0 0 0 0 4.4868 -3.1364 -2.1105 H 0 0 0 0 0 0 0 0 0 0 0 0 5.9430 -2.8455 -1.1267 H 0 0 0 0 0 0 0 0 0 0 0 0 4.3373 -2.6296 -0.3996 H 0 0 0 0 0 0 0 0 0 0 0 0 5.2596 -1.0141 -2.8438 H 0 0 0 0 0 0 0 0 0 0 0 0 6.1165 0.6870 -1.3035 H 0 0 0 0 0 0 0 0 0 0 0 0 6.8171 -0.8903 -0.8015 H 0 0 0 0 0 0 0 0 0 0 0 0 6.0255 0.2616 1.1693 H 0 0 0 0 0 0 0 0 0 0 0 0 5.1418 -1.2614 0.8772 H 0 0 0 0 0 0 0 0 0 0 0 0 2.9282 -0.5686 -2.5380 H 0 0 0 0 0 0 0 0 0 0 0 0 1.9565 1.9556 -0.2615 H 0 0 0 0 0 0 0 0 0 0 0 0 1.5195 1.5833 -2.5264 H 0 0 0 0 0 0 0 0 0 0 0 0 0.8937 -0.1242 -2.2656 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.8260 1.5327 -2.5179 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.2196 2.4214 -1.1103 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.6959 -0.5961 -1.0258 H 0 0 0 0 0 0 0 0 0 0 0 0 1.9123 1.7868 1.9062 H 0 0 0 0 0 0 0 0 0 0 0 0 1.3896 0.2415 2.7629 H 0 0 0 0 0 0 0 0 0 0 0 0 3.3593 -0.8977 2.0998 H 0 0 0 0 0 0 0 0 0 0 0 0 3.8136 0.7167 2.6731 H 0 0 0 0 0 0 0 0 0 0 0 0 1.1196 -1.7375 1.5678 H 0 0 0 0 0 0 0 0 0 0 0 0 2.4063 -1.4593 0.3863 H 0 0 0 0 0 0 0 0 0 0 0 0 0.7789 -1.7705 -0.2536 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.5510 2.1856 1.5561 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.0616 1.7707 2.4042 H 0 0 0 0 0 0 0 0 0 0 0 0 0.0268 2.6958 0.8957 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.5011 -0.5090 2.6383 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.8520 -1.4891 1.1165 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.7601 0.6595 2.1570 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.8242 -1.1733 2.3609 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.4774 -1.5187 0.0456 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.2167 2.5432 -0.7160 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.6218 2.0338 0.3568 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.7618 2.0579 -1.4095 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.5026 0.4262 -2.8510 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.5565 -1.1935 -1.9843 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.6650 -1.0367 -2.8234 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.7435 0.7405 -2.7169 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.6074 0.7730 -0.5857 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.2121 -2.6951 -0.6719 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.3748 -2.8290 1.1631 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.8167 -2.4868 0.0570 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.2542 -0.6889 1.4086 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.2598 0.7678 1.5674 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.8207 -0.7674 2.4454 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.3185 -1.4106 -2.0186 H 0 0 0 0 0 0 0 0 0 0 0 0 5.0410 3.5795 -0.6579 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 1 0 3 4 1 0 4 5 1 0 5 6 1 0 6 7 2 0 6 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 13 16 1 6 12 17 1 1 12 18 1 0 18 19 1 0 19 20 1 0 20 21 1 0 21 22 1 1 21 23 1 0 23 24 1 0 24 25 1 0 25 26 1 0 26 27 1 0 26 28 1 0 25 29 1 0 5 30 1 1 30 31 2 0 30 32 1 0 7 2 1 0 13 8 1 0 26 20 1 0 15 5 1 0 21 11 1 0 1 33 1 0 1 34 1 0 1 35 1 0 2 36 1 6 3 37 1 0 3 38 1 0 4 39 1 0 4 40 1 0 7 41 1 0 8 42 1 1 9 43 1 0 9 44 1 0 10 45 1 0 10 46 1 0 11 47 1 6 14 48 1 0 14 49 1 0 15 50 1 0 15 51 1 0 16 52 1 0 16 53 1 0 16 54 1 0 17 55 1 0 17 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 6 22 63 1 0 22 64 1 0 22 65 1 0 23 66 1 0 23 67 1 0 24 68 1 0 24 69 1 0 25 70 1 1 27 71 1 0 27 72 1 0 27 73 1 0 28 74 1 0 28 75 1 0 28 76 1 0 29 77 1 0 32 78 1 0 M END

Standard InCHIKey	PAUZLXLZBFVJQL-OOQZTYGSSA-N
Standard InCHI	InChI=1S/C29H46O3/c1-18-9-14-29(24(31)32)16-15-27(5)19(20(29)17-18)7-8-22-26(4)12-11-23(30)25(2,3)21(26)10-13-28(22,27)6/h17-19,21-23,30H,7-16H2,1-6H3,(H,31,32)/t18-,19-,21+,22-,23-,26+,27-,28-,29+/m1/s1
SMILES	C[C@@H]1CC[C@]2(C(=C1)[C@H]1CC[C@H]3[C@@]([C@@]1(CC2)C)(C)CC[C@@H]1[C@]3(C)CC[C@H](C1(C)C)O)C(=O)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	442.34	Volume:	488.455 ? Van der Waals volume.
Dense:	0.906	LogP:	4.38 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	3.599 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-4.295 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	1.0	Rigid Bonds:	27.0
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:	0.437	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	4.768	Fsp³:	0.897
MCE-18:	100.909 ? 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:	0.881	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:	0.0 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.483	Promiscuous compounds:	0.149

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.496	MDCK Permeability:	-5.054
Pgp-inhibitor:	0.022	Pgp-substrate:	0.012
PAMPA:	1.0 ? 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):	0.001
20% Bioavailability (F20%):	0.321	30% Bioavailability (F30%):	0.078
50% Bioavailability (F50%):	0.952

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.041	MRP1:	0.794
Plasma Protein Binding (PPB):	93.974%	Volume Distribution (VD):	-0.21
Fu:	6.961% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	1.0
OATP1B3 inhibitor:	0.87	BCRP inhibitor:	0.408
BSEP inhibitor:	0.976

ADMET: Metabolism

CYP1A2-inhibitor:	0.0	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	0.776	CYP2C19-substrate:	0.007
CYP2C9-inhibitor:	0.016	CYP2C9-substrate:	0.002
CYP2D6-inhibitor:	0.053	CYP2D6-substrate:	0.0
CYP3A4-inhibitor:	0.732	CYP3A4-substrate:	0.002
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.005
HLM stability:	0.161 ? 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):

5.354

Half-life (T1/2):

0.967

ADMET: Toxicity

hERG Blockers:	0.007	hERG Blockers (10um):	0.013
Human Hepatotoxicity (H-HT):	0.556	Drug-induced Liver Injury (DILI):	0.208
AMES Toxicity:	0.231	Rat Oral Acute Toxicity:	0.125
Maximum Recommended Daily Dose:	0.566	Skin Sensitization:	0.978
Carcinogencity:	0.834	Eye Corrosion:	0.356
Eye Irritation:	0.915	Respiratory Toxicity:	0.918
Drug-induced Neurotoxicity:	0.0	Ototoxicity:	0.436
Hematotoxicity:	0.441	Drug-induced Nephrotoxicity:	0.905
Genotoxicity:	0.071	RPMI-8226 Immunitoxicity:	0.048
A549 Cytotoxicity:	0.056	Hek293 Cytotoxicity:	0.084
BCF:	1.423 ? 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:	3.859 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.394 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.713 ? 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
NPO10810	Acridocarpus vivy	Species	Malpighiaceae	Eukaryota	n.a.	Madagascar rain forest	n.a.	PMID[15217279]
NPO10810	Acridocarpus vivy	Species	Malpighiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO10810	Acridocarpus vivy	Species	Malpighiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]

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
NPT179	Cell line	A2780	Homo sapiens	IC50	=	5.9	ug.mL-1	PMID[9214736]

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 NPC474512 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	22093
0.1-0.2	23455
0.2-0.3	3567
0.3-0.4	614
0.4-0.5	112
0.5-0.6	9
0.6-0.7	5
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
0.7833	Intermediate Similarity	NPC181225
0.7188	Intermediate Similarity	NPC474511
0.6719	Remote Similarity	NPC474686
0.6615	Remote Similarity	NPC474474
0.6567	Remote Similarity	NPC474728
0.6286	Remote Similarity	NPC474700
0.6119	Remote Similarity	NPC143232
0.5588	Remote Similarity	NPC264317
0.5588	Remote Similarity	NPC294438
0.5571	Remote Similarity	NPC18064
0.5522	Remote Similarity	NPC472608
0.5362	Remote Similarity	NPC30583
0.5352	Remote Similarity	NPC16377
0.5294	Remote Similarity	NPC69101
0.5286	Remote Similarity	NPC476071
0.5156	Remote Similarity	NPC212733

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC474512 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	6277
0.1-0.2	2807
0.2-0.3	61
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
0.5588	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