NPASS Compound

Natural Product: NPC44963

Natural Product ID	NPC44963
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	Hyperforin
IUPAC Name	(1R,5R,6R,7S)-2-hydroxy-6-methyl-1,3,7-tris(3-methylbut-2-enyl)-6-(4-methylpent-3-enyl)-5-(2-methylpropanoyl)bicyclo[3.3.1]non-2-ene-4,9-dione
Synonyms	Hyperforin
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL501711
PubChem CID	441298
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000012] Lipids and lipid-like molecules [CHEMONTID:0000259] Prenol lipids [CHEMONTID:0001549] Monoterpenoids [CHEMONTID:0001564] Bicyclic monoterpenoids

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 91 92 0 0 0 0 0 0 0 0999 V2000 3.8480 -2.1281 4.4615 C 0 0 0 0 0 0 0 0 0 0 0 0 2.9771 -2.2375 3.2671 C 0 0 0 0 0 0 0 0 0 0 0 0 3.3380 -1.6531 2.1520 C 0 0 0 0 0 0 0 0 0 0 0 0 2.5276 -1.6932 0.8590 C 0 0 0 0 0 0 0 0 0 0 0 0 2.2120 -0.3370 0.4007 C 0 0 0 0 0 0 0 0 0 0 0 0 1.4969 -0.1047 -0.9157 C 0 0 2 0 0 0 0 0 0 0 0 0 2.4312 -0.8249 -1.8800 C 0 0 0 0 0 0 0 0 0 0 0 0 1.6289 1.3947 -1.0691 C 0 0 1 0 0 0 0 0 0 0 0 0 1.5586 2.1655 -2.2584 C 0 0 0 0 0 0 0 0 0 0 0 0 2.4026 2.0864 -3.4248 C 0 0 0 0 0 0 0 0 0 0 0 0 3.2347 3.0688 -3.8296 C 0 0 0 0 0 0 0 0 0 0 0 0 4.0312 2.8284 -5.0476 C 0 0 0 0 0 0 0 0 0 0 0 0 3.3836 4.3586 -3.1176 C 0 0 0 0 0 0 0 0 0 0 0 0 0.7345 2.0539 -0.0327 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.6795 1.5628 -0.0639 C 0 0 2 0 0 0 0 0 0 0 0 0 -1.7049 2.6596 -0.1446 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.6477 3.5919 1.0031 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.6457 3.8164 1.8465 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.9686 3.1147 1.6994 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.5152 4.7694 2.9804 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.9988 0.7878 1.1932 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.1440 -0.5426 1.1828 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.9771 -1.1868 2.2654 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.0941 -1.8908 1.5326 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.3430 -3.1813 1.6644 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.4541 -3.8246 0.9178 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.5124 -3.9902 2.5819 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.5207 -1.3214 0.1142 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.5613 -2.5761 0.1879 O 0 0 0 0 0 0 0 0 0 0 0 0 0.1362 -0.6027 -1.0380 C 0 0 2 0 0 0 0 0 0 0 0 0 -0.1994 -1.4315 -2.2326 C 0 0 0 0 0 0 0 0 0 0 0 0 0.5261 -1.6567 -3.1500 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.5515 -2.0541 -2.3240 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.3498 -1.5591 -3.5114 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.3344 -3.5458 -2.5428 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.7936 0.6131 -1.1692 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.5148 0.7344 -2.0800 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.1545 1.4334 2.4131 O 0 0 0 0 0 0 0 0 0 0 0 0 1.7114 -3.0126 3.3460 C 0 0 0 0 0 0 0 0 0 0 0 0 3.6205 -2.9053 5.2222 H 0 0 0 0 0 0 0 0 0 0 0 0 4.9321 -2.2391 4.2222 H 0 0 0 0 0 0 0 0 0 0 0 0 3.6936 -1.1076 4.8789 H 0 0 0 0 0 0 0 0 0 0 0 0 4.2682 -1.1016 2.1283 H 0 0 0 0 0 0 0 0 0 0 0 0 3.0984 -2.3255 0.1513 H 0 0 0 0 0 0 0 0 0 0 0 0 1.6640 -2.2889 1.1773 H 0 0 0 0 0 0 0 0 0 0 0 0 1.7458 0.2046 1.2594 H 0 0 0 0 0 0 0 0 0 0 0 0 3.2345 0.1892 0.3543 H 0 0 0 0 0 0 0 0 0 0 0 0 2.3064 -1.9141 -1.7139 H 0 0 0 0 0 0 0 0 0 0 0 0 2.3936 -0.6241 -2.9064 H 0 0 0 0 0 0 0 0 0 0 0 0 3.5072 -0.6076 -1.5730 H 0 0 0 0 0 0 0 0 0 0 0 0 2.6789 1.5988 -0.6161 H 0 0 0 0 0 0 0 0 0 0 0 0 1.6729 3.2747 -1.9300 H 0 0 0 0 0 0 0 0 0 0 0 0 0.5032 2.2600 -2.6814 H 0 0 0 0 0 0 0 0 0 0 0 0 2.3924 1.2219 -4.0724 H 0 0 0 0 0 0 0 0 0 0 0 0 3.3840 2.8239 -5.9729 H 0 0 0 0 0 0 0 0 0 0 0 0 4.4966 1.8053 -5.0502 H 0 0 0 0 0 0 0 0 0 0 0 0 4.7954 3.5894 -5.2265 H 0 0 0 0 0 0 0 0 0 0 0 0 2.5848 5.0884 -3.3808 H 0 0 0 0 0 0 0 0 0 0 0 0 3.4765 4.2105 -2.0215 H 0 0 0 0 0 0 0 0 0 0 0 0 4.3398 4.8297 -3.4296 H 0 0 0 0 0 0 0 0 0 0 0 0 0.7108 3.1487 -0.2995 H 0 0 0 0 0 0 0 0 0 0 0 0 1.1959 2.0499 0.9747 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.7229 2.2167 -0.1671 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.6312 3.2281 -1.1129 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.7289 4.1338 1.1740 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.7937 2.0103 1.5523 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.6252 3.3055 2.5516 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.4670 3.4560 0.7582 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.4747 5.2565 3.1913 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.7669 5.5555 2.7963 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.2678 4.1612 3.8949 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.4356 -0.3746 2.8526 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.4255 -1.9107 2.8552 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.7417 -1.3230 0.8536 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.3089 -4.0802 1.5888 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.8425 -3.1086 0.1761 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.1252 -4.7243 0.3571 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.4388 -3.5064 3.6003 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.5209 -4.1655 2.1699 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.0571 -4.9541 2.7996 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.1684 -1.8589 -1.4239 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.7196 -2.4076 -4.1366 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.2625 -0.9947 -3.2294 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.7074 -0.9644 -4.1908 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.3198 -3.7112 -3.6445 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.1408 -4.0965 -2.0428 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.3724 -3.9144 -2.1756 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.3339 1.5974 3.0088 H 0 0 0 0 0 0 0 0 0 0 0 0 1.5606 -3.3167 4.4006 H 0 0 0 0 0 0 0 0 0 0 0 0 1.7797 -3.9680 2.7713 H 0 0 0 0 0 0 0 0 0 0 0 0 0.8501 -2.4071 3.0397 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 2 3 3 4 1 0 4 5 1 0 6 5 1 1 6 7 1 0 6 8 1 0 8 9 1 0 9 10 1 0 10 11 2 3 11 12 1 0 11 13 1 0 8 14 1 0 14 15 1 0 15 16 1 6 16 17 1 0 17 18 2 3 18 19 1 0 18 20 1 0 15 21 1 0 21 22 2 0 22 23 1 0 23 24 1 0 24 25 2 3 25 26 1 0 25 27 1 0 22 28 1 0 28 29 2 0 28 30 1 0 30 31 1 6 31 32 2 0 31 33 1 0 33 34 1 0 33 35 1 0 30 36 1 0 36 37 2 0 21 38 1 0 2 39 1 0 30 6 1 0 36 15 1 0 1 40 1 0 1 41 1 0 1 42 1 0 3 43 1 0 4 44 1 0 4 45 1 0 5 46 1 0 5 47 1 0 7 48 1 0 7 49 1 0 7 50 1 0 8 51 1 1 9 52 1 0 9 53 1 0 10 54 1 0 12 55 1 0 12 56 1 0 12 57 1 0 13 58 1 0 13 59 1 0 13 60 1 0 14 61 1 0 14 62 1 0 16 63 1 0 16 64 1 0 17 65 1 0 19 66 1 0 19 67 1 0 19 68 1 0 20 69 1 0 20 70 1 0 20 71 1 0 23 72 1 0 23 73 1 0 24 74 1 0 26 75 1 0 26 76 1 0 26 77 1 0 27 78 1 0 27 79 1 0 27 80 1 0 33 81 1 0 34 82 1 0 34 83 1 0 34 84 1 0 35 85 1 0 35 86 1 0 35 87 1 0 38 88 1 0 39 89 1 0 39 90 1 0 39 91 1 0 M END

Standard InCHIKey	KGSZHKRKHXOAMG-HQKKAZOISA-N
Standard InCHI	InChI=1S/C35H52O4/c1-22(2)13-12-19-33(11)27(16-14-23(3)4)21-34(20-18-25(7)8)30(37)28(17-15-24(5)6)31(38)35(33,32(34)39)29(36)26(9)10/h13-15,18,26-27,37H,12,16-17,19-21H2,1-11H3/t27-,33+,34+,35-/m0/s1
SMILES	CC(=CCC[C@]1(C)[C@@H](CC=C(C)C)C[C@]2(CC=C(C)C)C(=C(CC=C(C)C)C(=O)[C@@]1(C(=O)C(C)C)C2=O)O)C

Calculated Properties

Physi-Chem Properties

Molecular Weight:	536.39	Volume:	610.872 ? Van der Waals volume.
Dense:	0.878	LogP:	7.177 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	4.818 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-5.808 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	11.0	Rigid Bonds:	17.0
TPSA:	71.44 ? Topological Polar Surface Area.	H-Bond Acceptor:	4.0
H-Bond Donor:	1.0	Rings:	2.0
Heavy Atoms:	4.0

MedChem Properties

QED Drug-Likeness Score:	0.211	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	5.656	Fsp³:	0.629
MCE-18:	56.561 ? MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.	Lipinski Rule-of-5:	Accepted
Pfizer Rule:	Accepted	GSK Rule:	Accepted
Golden Triangle Rule:	Accepted	BMS Rule:	0
Chelating Alert:	1	PAINS Alert:	0
Colloidal aggregators:	0.979	Fluc inhibitor:	0.028 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.095 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.297 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.657	Promiscuous compounds:	0.023

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-4.555	MDCK Permeability:	-4.675
Pgp-inhibitor:	0.769	Pgp-substrate:	0.001
PAMPA:	0.324 ? 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%):	0.005	30% Bioavailability (F30%):	0.0
50% Bioavailability (F50%):	0.463

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.013	MRP1:	0.999
Plasma Protein Binding (PPB):	89.531%	Volume Distribution (VD):	0.294
Fu:	11.578% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.997
OATP1B3 inhibitor:	0.616	BCRP inhibitor:	0.002
BSEP inhibitor:	0.997

ADMET: Metabolism

CYP1A2-inhibitor:	0.101	CYP1A2-substrate:	1.0
CYP2C19-inhibitor:	1.0	CYP2C19-substrate:	1.0
CYP2C9-inhibitor:	0.0	CYP2C9-substrate:	0.001
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.788
CYP3A4-inhibitor:	0.999	CYP3A4-substrate:	1.0
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	1.0
HLM stability:	1.0 ? 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):

5.061

Half-life (T1/2):

0.803

ADMET: Toxicity

hERG Blockers:	0.049	hERG Blockers (10um):	0.202
Human Hepatotoxicity (H-HT):	0.745	Drug-induced Liver Injury (DILI):	0.273
AMES Toxicity:	0.214	Rat Oral Acute Toxicity:	0.525
Maximum Recommended Daily Dose:	0.177	Skin Sensitization:	0.952
Carcinogencity:	0.702	Eye Corrosion:	0.005
Eye Irritation:	0.161	Respiratory Toxicity:	0.903
Drug-induced Neurotoxicity:	0.092	Ototoxicity:	0.616
Hematotoxicity:	0.524	Drug-induced Nephrotoxicity:	0.807
Genotoxicity:	0.734	RPMI-8226 Immunitoxicity:	0.029
A549 Cytotoxicity:	0.031	Hek293 Cytotoxicity:	0.032
BCF:	2.223 ? 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:	5.339 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	7.197 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	7.462 ? 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
NPO4391	Hypericum perforatum	Species	Hypericaceae	Eukaryota	n.a.	n.a.	n.a.	DOI[10.1007/s11240-015-0798-z]
NPO4391	Hypericum perforatum	Species	Hypericaceae	Eukaryota	n.a.	n.a.	n.a.	DOI[10.1016/j.fitote.2006.01.011]
NPO4391	Hypericum perforatum	Species	Hypericaceae	Eukaryota	n.a.	n.a.	n.a.	DOI[10.1016/j.jarmap.2018.11.004]
NPO4391	Hypericum perforatum	Species	Hypericaceae	Eukaryota	n.a.	n.a.	n.a.	DOI[10.1016/j.plaphy.2005.07.013]
NPO4391	Hypericum perforatum	Species	Hypericaceae	Eukaryota	n.a.	n.a.	n.a.	DOI[10.1078/0176-1617-00195]
NPO4391	Hypericum perforatum	Species	Hypericaceae	Eukaryota	n.a.	n.a.	n.a.	DOI[10.1155/2014/609649]
NPO4391	Hypericum perforatum	Species	Hypericaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[10757735]
NPO4391	Hypericum perforatum	Species	Hypericaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[14735439]
NPO4391	Hypericum perforatum	Species	Hypericaceae	Eukaryota	n.a.	callus	n.a.	PMID[15715262]
NPO4391	Hypericum perforatum	Species	Hypericaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[18220354]
NPO19915	Hypericum henryi	Species	Hypericaceae	Eukaryota	aerial parts	Yunnan, China	n.a.	PMID[25871261]
NPO4391	Hypericum perforatum	Species	Hypericaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[28445039]
NPO4391	Hypericum perforatum	Species	Hypericaceae	Eukaryota	Roots	n.a.	n.a.	PMID[30024167]
NPO4391	Hypericum perforatum	Species	Hypericaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[32560389]
NPO4391	Hypericum perforatum	Species	Hypericaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[36336219]
NPO4391	Hypericum perforatum	Species	Hypericaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[38217369]
NPO19915	Hypericum henryi	Species	Hypericaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO4391	Hypericum perforatum	Species	Hypericaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO16145	Apocynum venetum	Species	Apocynaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO16145	Apocynum venetum	Species	Apocynaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO4391	Hypericum perforatum	Species	Hypericaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO19915	Hypericum henryi	Species	Hypericaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO16145	Apocynum venetum	Species	Apocynaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO4391	Hypericum perforatum	Species	Hypericaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO4391	Hypericum perforatum	Species	Hypericaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO16145	Apocynum venetum	Species	Apocynaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO16145	Apocynum venetum	Species	Apocynaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO4391	Hypericum perforatum	Species	Hypericaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO19915	Hypericum henryi	Species	Hypericaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO4391	Hypericum perforatum	Species	Hypericaceae	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
NPO4391	Hypericum perforatum	n.a.	Shoots	28.13 Â± 4.53	n.a.	n.a.	mg/g	PMID[36336219]
NPO4391	Hypericum perforatum	n.a.	Shoots	15.44 Â± 3.49	n.a.	n.a.	mg/g	PMID[36336219]

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	8
Ki	2
Potency	11
Kd	1
Inhibition	1
Activity	1

Activity Type	# Activity
Individual protein	13
Cell line	5
Single protein	1
Organism	1
Non-molecular	1
Others	3

Molecular-level activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT1072	Individual protein	Serotonin transporter	Rattus norvegicus	IC50	=	1.1	ug.mL-1	PMID[11975475]
NPT109	Individual protein	Cytochrome P450 3A4	Homo sapiens	IC50	=	2300.0	nM	PMID[20408551]
NPT198	Individual protein	Vitamin D receptor	Homo sapiens	Potency	n.a.	28183.8	nM	PubChem BioAssay data set
NPT29060	Single protein	Dihydrolipoyllysine-residue acetyltransferase component of pyruvate dehydrogenase complex, mitochondrial	Homo sapiens	Kd	=	578.0	nM	PMID[35489224]
NPT888	Individual protein	78 kDa glucose-regulated protein	Homo sapiens	Potency	n.a.	50118.7	nM	PubChem BioAssay data set
NPT93	Individual protein	Survival motor neuron protein	Homo sapiens	Potency	=	12589.3	nM	PubChem BioAssay data set
NPT51	Individual protein	Microtubule-associated protein tau	Homo sapiens	Potency	=	12589.3	nM	PubChem BioAssay data set
NPT51	Individual protein	Microtubule-associated protein tau	Homo sapiens	Potency	=	25118.9	nM	PubChem BioAssay data set
NPT583	Individual protein	Inositol monophosphatase 1	Rattus norvegicus	Potency	=	1778.3	nM	PubChem BioAssay data set
NPT543	Individual protein	Pregnane X receptor	Homo sapiens	Ki	=	27.0	nM	PMID[20408551]
NPT442	Individual protein	Ferritin light chain	Equus caballus	Potency	=	28183.8	nM	PubChem BioAssay data set
NPT443	Individual protein	Histone acetyltransferase GCN5	Homo sapiens	Potency	n.a.	28183.8	nM	PubChem BioAssay data set
NPT5	Individual protein	Histone-lysine N-methyltransferase, H3 lysine-9 specific 3	Homo sapiens	Potency	n.a.	17782.8	nM	PubChem BioAssay data set

In vitro activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT116	Cell line	HL-60	Homo sapiens	IC50	>	40000.0	nM	PMID[25871261]
NPT659	Cell line	SMMC-7721	Homo sapiens	IC50	>	40000.0	nM	PMID[25871261]
NPT81	Cell line	A549	Homo sapiens	IC50	>	40000.0	nM	PMID[25871261]
NPT83	Cell line	MCF7	Homo sapiens	IC50	>	40000.0	nM	PMID[25871261]
NPT660	Cell line	SW480	Homo sapiens	IC50	>	40000.0	nM	PMID[25871261]
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	IC50	=	2100.0	nM	PMID[23030826]
NPT2	Others	Unspecified	n.a.	Inhibition	=	20.0	%	PMID[23062825]
NPT2	Others	Unspecified	n.a.	Potency	n.a.	12589.3	nM	PubChem BioAssay data set
NPT2	Others	Unspecified	n.a.	Potency	n.a.	15848.9	nM	PubChem BioAssay data set

In vivo activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT32	Organism	Mus musculus	Mus musculus	Activity	=	-13.7	%	PMID[35489224]

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 NPC44963 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	23354
0.1-0.2	25439
0.2-0.3	914
0.3-0.4	89
0.4-0.5	51
0.5-0.6	7
0.6-0.7	2
0.7-0.8	0
0.8-0.85	0
0.85-0.9	1
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Natural Product ID
0.8868	High Similarity	NPC472684
0.65	Remote Similarity	NPC228644
0.6032	Remote Similarity	NPC483081
0.5224	Remote Similarity	NPC472733
0.5224	Remote Similarity	NPC472734
0.5217	Remote Similarity	NPC471331
0.5217	Remote Similarity	NPC99657
0.5217	Remote Similarity	NPC203388
0.5167	Remote Similarity	NPC600619
0.5072	Remote Similarity	NPC218855

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC44963 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	7610
0.1-0.2	1517
0.2-0.3	23
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