NPASS Compound

Natural Product: NPC196528

Natural Product ID	NPC196528
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	23,24-Dihydrocucurbitacin B
IUPAC Name	[(6R)-6-[(2S,8S,9R,10R,13R,14S,16R,17R)-2,16-dihydroxy-4,4,9,13,14-pentamethyl-3,11-dioxo-2,7,8,10,12,15,16,17-octahydro-1H-cyclopenta[a]phenanthren-17-yl]-6-hydroxy-2-methyl-5-oxoheptan-2-yl] acetate
Synonyms	23,24-Dihydrocucurbitacin B; Dihydrocucurbitacin B
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL553851
PubChem CID	267250
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000012] Lipids and lipid-like molecules [CHEMONTID:0000258] Steroids and steroid derivatives [CHEMONTID:0001686] Cucurbitacins

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 88 91 0 0 0 0 0 0 0 0999 V2000 8.2301 3.1890 -2.1345 C 0 0 0 0 0 0 0 0 0 0 0 0 7.5471 2.0932 -1.3637 C 0 0 0 0 0 0 0 0 0 0 0 0 7.6265 2.0356 -0.1320 O 0 0 0 0 0 0 0 0 0 0 0 0 6.8440 1.1774 -2.0854 O 0 0 0 0 0 0 0 0 0 0 0 0 6.1452 0.0936 -1.5239 C 0 0 0 0 0 0 0 0 0 0 0 0 5.0721 0.5609 -0.5897 C 0 0 0 0 0 0 0 0 0 0 0 0 4.3792 -0.6594 -0.0422 C 0 0 0 0 0 0 0 0 0 0 0 0 3.2848 -0.3235 0.9033 C 0 0 0 0 0 0 0 0 0 0 0 0 3.0853 0.8386 1.1108 O 0 0 0 0 0 0 0 0 0 0 0 0 2.4580 -1.3497 1.5769 C 0 0 1 0 0 0 0 0 0 0 0 0 1.0626 -1.4870 1.1367 C 0 0 1 0 0 0 0 0 0 0 0 0 0.4365 -2.6195 1.9264 C 0 0 2 0 0 0 0 0 0 0 0 0 0.5982 -3.8729 1.3682 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.0289 -2.2604 2.1038 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.2215 -1.2058 1.0469 C 0 0 2 0 0 0 0 0 0 0 0 0 0.0727 -0.3825 1.2324 C 0 0 1 0 0 0 0 0 0 0 0 0 0.0470 0.3853 2.5046 C 0 0 0 0 0 0 0 0 0 0 0 0 0.0255 0.5948 0.1010 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.3232 1.0456 -0.3169 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.3535 1.7688 -1.3026 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.5986 0.7189 0.3191 C 0 0 2 0 0 0 0 0 0 0 0 0 -2.4209 -0.3488 1.3392 C 0 0 1 0 0 0 0 0 0 0 0 0 -3.6411 -1.1424 1.6664 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.8862 -0.4082 1.3069 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.9546 0.3260 0.2012 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.7132 0.3473 -0.6156 C 0 0 1 0 0 0 0 0 0 0 0 0 -3.7943 1.1914 -1.8400 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.1437 0.9341 -2.5051 C 0 0 2 0 0 0 0 0 0 0 0 0 -5.2394 1.6081 -3.7029 O 0 0 0 0 0 0 0 0 0 0 0 0 -6.2624 1.2707 -1.5916 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.2554 1.7753 -2.1107 O 0 0 0 0 0 0 0 0 0 0 0 0 -6.2184 1.0254 -0.1281 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.4282 0.1454 0.1956 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.4288 2.2975 0.6629 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.0962 2.0199 0.9694 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.2709 -1.8807 -0.2652 C 0 0 0 0 0 0 0 0 0 0 0 0 3.0315 -2.5838 1.1055 O 0 0 0 0 0 0 0 0 0 0 0 0 2.7251 -1.4184 3.0582 C 0 0 0 0 0 0 0 0 0 0 0 0 5.6029 -0.7267 -2.6735 C 0 0 0 0 0 0 0 0 0 0 0 0 7.1579 -0.7968 -0.8113 C 0 0 0 0 0 0 0 0 0 0 0 0 9.1661 2.7685 -2.5001 H 0 0 0 0 0 0 0 0 0 0 0 0 7.5885 3.4594 -2.9829 H 0 0 0 0 0 0 0 0 0 0 0 0 8.3414 4.0730 -1.4816 H 0 0 0 0 0 0 0 0 0 0 0 0 5.5637 1.0987 0.2438 H 0 0 0 0 0 0 0 0 0 0 0 0 4.3770 1.2400 -1.1090 H 0 0 0 0 0 0 0 0 0 0 0 0 4.0728 -1.2806 -0.8820 H 0 0 0 0 0 0 0 0 0 0 0 0 5.1529 -1.2316 0.5352 H 0 0 0 0 0 0 0 0 0 0 0 0 1.1462 -1.7281 0.0334 H 0 0 0 0 0 0 0 0 0 0 0 0 0.8313 -2.7178 2.9525 H 0 0 0 0 0 0 0 0 0 0 0 0 1.1939 -3.8170 0.6013 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.2878 -1.9537 3.1157 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.6204 -3.1625 1.7771 H 0 0 0 0 0 0 0 0 0 0 0 0 1.0609 0.7354 2.7358 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.5111 1.3551 2.3691 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.4498 -0.1171 3.3512 H 0 0 0 0 0 0 0 0 0 0 0 0 0.5355 1.5491 0.4345 H 0 0 0 0 0 0 0 0 0 0 0 0 0.5802 0.1824 -0.7904 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.1579 0.1980 2.2983 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.6780 -1.3475 2.7738 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.6076 -2.1372 1.1600 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.7816 -0.4412 1.9261 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.6521 -0.7069 -0.9768 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.0452 0.7717 -2.5672 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.7075 2.2644 -1.7167 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.2058 -0.1545 -2.7171 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.1566 1.6993 -4.0124 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.0831 -0.9044 0.0355 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.6358 0.2507 1.2700 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.2825 0.3538 -0.4482 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.9494 3.1659 0.1636 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.0759 2.1343 1.6983 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.5358 2.4761 0.7527 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.6122 2.6742 0.2476 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.7024 1.8302 1.8613 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.1976 2.6021 1.2988 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.5149 -2.6274 -0.4880 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.3211 -1.2408 -1.1636 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.2475 -2.4677 -0.2959 H 0 0 0 0 0 0 0 0 0 0 0 0 3.9176 -2.7084 1.5150 H 0 0 0 0 0 0 0 0 0 0 0 0 3.1387 -2.3917 3.4005 H 0 0 0 0 0 0 0 0 0 0 0 0 1.8840 -1.2146 3.7157 H 0 0 0 0 0 0 0 0 0 0 0 0 3.5216 -0.6742 3.3677 H 0 0 0 0 0 0 0 0 0 0 0 0 4.7468 -0.2200 -3.1707 H 0 0 0 0 0 0 0 0 0 0 0 0 6.4199 -0.7605 -3.4387 H 0 0 0 0 0 0 0 0 0 0 0 0 5.3838 -1.7628 -2.4032 H 0 0 0 0 0 0 0 0 0 0 0 0 6.9007 -1.8757 -0.9818 H 0 0 0 0 0 0 0 0 0 0 0 0 7.1912 -0.5986 0.2760 H 0 0 0 0 0 0 0 0 0 0 0 0 8.1524 -0.6160 -1.2434 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 2 0 8 10 1 0 10 11 1 0 11 12 1 0 12 13 1 0 12 14 1 0 14 15 1 0 15 16 1 0 16 17 1 1 16 18 1 0 18 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 2 0 25 26 1 0 26 27 1 0 27 28 1 0 28 29 1 0 28 30 1 0 30 31 2 0 30 32 1 0 32 33 1 0 32 34 1 0 21 35 1 1 15 36 1 6 10 37 1 6 10 38 1 0 5 39 1 0 5 40 1 0 16 11 1 0 26 21 1 0 22 15 1 0 32 25 1 0 1 41 1 0 1 42 1 0 1 43 1 0 6 44 1 0 6 45 1 0 7 46 1 0 7 47 1 0 11 48 1 6 12 49 1 1 13 50 1 0 14 51 1 0 14 52 1 0 17 53 1 0 17 54 1 0 17 55 1 0 18 56 1 0 18 57 1 0 22 58 1 1 23 59 1 0 23 60 1 0 24 61 1 0 26 62 1 6 27 63 1 0 27 64 1 0 28 65 1 6 29 66 1 0 33 67 1 0 33 68 1 0 33 69 1 0 34 70 1 0 34 71 1 0 34 72 1 0 35 73 1 0 35 74 1 0 35 75 1 0 36 76 1 0 36 77 1 0 36 78 1 0 37 79 1 0 38 80 1 0 38 81 1 0 38 82 1 0 39 83 1 0 39 84 1 0 39 85 1 0 40 86 1 0 40 87 1 0 40 88 1 0 M END

Standard InCHIKey	QZJJDOYZVRUEDY-NRNCYQGDSA-N
Standard InCHI	InChI=1S/C32H48O8/c1-17(33)40-27(2,3)13-12-23(36)32(9,39)25-21(35)15-29(6)22-11-10-18-19(14-20(34)26(38)28(18,4)5)31(22,8)24(37)16-30(25,29)7/h10,19-22,25,34-35,39H,11-16H2,1-9H3/t19-,20+,21-,22+,25+,29+,30-,31+,32+/m1/s1
SMILES	CC(=O)OC(CCC(=O)[C@@]([C@H]1[C@H](O)C[C@@]2([C@]1(C)CC(=O)[C@@]1([C@H]2CC=C2[C@H]1C[C@H](O)C(=O)C2(C)C)C)C)(O)C)(C)C

Calculated Properties

Physi-Chem Properties

Molecular Weight:	560.33	Volume:	584.942 ? Van der Waals volume.
Dense:	0.958	LogP:	2.075 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	2.399 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-4.013 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	7.0	Rigid Bonds:	24.0
TPSA:	138.2 ? Topological Polar Surface Area.	H-Bond Acceptor:	8.0
H-Bond Donor:	3.0	Rings:	4.0
Heavy Atoms:	8.0

MedChem Properties

QED Drug-Likeness Score:	0.33	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	5.362	Fsp³:	0.812
MCE-18:	97.931 ? 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:	0.831	Fluc inhibitor:	0.0 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.022 ? 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:	0.253	Promiscuous compounds:	0.845

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.066	MDCK Permeability:	-4.72
Pgp-inhibitor:	0.298	Pgp-substrate:	0.045
PAMPA:	0.987 ? 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%):	0.157	30% Bioavailability (F30%):	0.574
50% Bioavailability (F50%):	0.998

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.018	MRP1:	0.997
Plasma Protein Binding (PPB):	83.999%	Volume Distribution (VD):	-0.006
Fu:	18.656% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	1.0
OATP1B3 inhibitor:	1.0	BCRP inhibitor:	0.341
BSEP inhibitor:	0.998

ADMET: Metabolism

CYP1A2-inhibitor:	0.002	CYP1A2-substrate:	0.007
CYP2C19-inhibitor:	0.015	CYP2C19-substrate:	0.306
CYP2C9-inhibitor:	0.0	CYP2C9-substrate:	0.058
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.975
CYP3A4-inhibitor:	0.999	CYP3A4-substrate:	1.0
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	1.0
HLM stability:	0.931 ? 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):

5.677

Half-life (T1/2):

1.09

ADMET: Toxicity

hERG Blockers:	0.013	hERG Blockers (10um):	0.108
Human Hepatotoxicity (H-HT):	0.493	Drug-induced Liver Injury (DILI):	0.655
AMES Toxicity:	0.708	Rat Oral Acute Toxicity:	0.758
Maximum Recommended Daily Dose:	0.796	Skin Sensitization:	0.988
Carcinogencity:	0.804	Eye Corrosion:	0.0
Eye Irritation:	0.037	Respiratory Toxicity:	0.778
Drug-induced Neurotoxicity:	0.48	Ototoxicity:	0.475
Hematotoxicity:	0.788	Drug-induced Nephrotoxicity:	0.951
Genotoxicity:	0.999	RPMI-8226 Immunitoxicity:	0.419
A549 Cytotoxicity:	0.383	Hek293 Cytotoxicity:	0.455
BCF:	0.512 ? 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:	3.196 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.734 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.128 ? 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
NPO40156	Hemsleya endecaphylla	Species	Cucurbitaceae	Eukaryota	Tubers	n.a.	n.a.	PMID[18088099]
NPO13450	Cucumis melo	Species	Cucurbitaceae	Eukaryota	Stems	n.a.	n.a.	PMID[19348465]
NPO1592	Citrullus colocynthis	Species	Cucurbitaceae	Eukaryota	Fruits	n.a.	n.a.	PMID[30183289]
NPO21876	Trichosanthes cucumeroides	Species	Cucurbitaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[33269591]
NPO1592	Citrullus colocynthis	Species	Cucurbitaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[37893598]
NPO1592	Citrullus colocynthis	Species	Cucurbitaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO21876	Trichosanthes cucumeroides	Species	Cucurbitaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO13450	Cucumis melo	Species	Cucurbitaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO13450	Cucumis melo	Species	Cucurbitaceae	Eukaryota	Seed	n.a.	n.a.	Database[FooDB]
NPO13450	Cucumis melo	Species	Cucurbitaceae	Eukaryota	Fruit	n.a.	n.a.	Database[FooDB]
NPO13450	Cucumis melo	Species	Cucurbitaceae	Eukaryota	Cotyledon	n.a.	n.a.	Database[FooDB]
NPO13450	Cucumis melo	Species	Cucurbitaceae	Eukaryota		n.a.	n.a.	Database[FooDB]
NPO13450	Cucumis melo	Species	Cucurbitaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO21876	Trichosanthes cucumeroides	Species	Cucurbitaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO1592	Citrullus colocynthis	Species	Cucurbitaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO1592	Citrullus colocynthis	Species	Cucurbitaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO27538	Hemsleya macrosperma	Species	Cucurbitaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO13450	Cucumis melo	Species	Cucurbitaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO21876	Trichosanthes cucumeroides	Species	Cucurbitaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO1592	Citrullus colocynthis	Species	Cucurbitaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO27538	Hemsleya macrosperma	Species	Cucurbitaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO21876	Trichosanthes cucumeroides	Species	Cucurbitaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO13450	Cucumis melo	Species	Cucurbitaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO27538	Hemsleya macrosperma	Species	Cucurbitaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO1592	Citrullus colocynthis	Species	Cucurbitaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO21876	Trichosanthes cucumeroides	Species	Cucurbitaceae	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
EC50	1
IC50	3
Ratio IC50	1
CC50	1
Ratio CC50/EC50	1

Activity Type	# Activity
Cell line	5
Organism	1
Others	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
NPT81	Cell line	A549	Homo sapiens	IC50	=	19910.0	nM	PMID[22472043]
NPT81	Cell line	A549	Homo sapiens	IC50	=	12090.0	nM	PMID[22472043]
NPT81	Cell line	A549	Homo sapiens	Ratio IC50	=	1.6	n.a.	PMID[22472043]
NPT83	Cell line	MCF7	Homo sapiens	IC50	=	46300.0	nM	PMID[25756299]
NPT1452	Cell line	C8166	Homo sapiens	CC50	=	25.5	ug.mL-1	PMID[18088099]
NPT24	Organism	Human immunodeficiency virus 1	Human immunodeficiency virus 1	EC50	=	4.2	ug.mL-1	PMID[18088099]
NPT2	Others	Unspecified	n.a.	Ratio CC50/EC50	=	6.1	n.a.	PMID[18088099]

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 NPC196528 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	19201
0.1-0.2	28481
0.2-0.3	2098
0.3-0.4	35
0.4-0.5	17
0.5-0.6	13
0.6-0.7	4
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
0.7826	Intermediate Similarity	NPC486346
0.7727	Intermediate Similarity	NPC49371
0.7727	Intermediate Similarity	NPC479419
0.7714	Intermediate Similarity	NPC280782
0.7222	Intermediate Similarity	NPC100267
0.7222	Intermediate Similarity	NPC475524
0.7206	Intermediate Similarity	NPC117185
0.6986	Remote Similarity	NPC304495
0.6714	Remote Similarity	NPC311612
0.6429	Remote Similarity	NPC486351
0.625	Remote Similarity	NPC479420
0.5949	Remote Similarity	NPC239273
0.5811	Remote Similarity	NPC191892
0.5652	Remote Similarity	NPC488647
0.5625	Remote Similarity	NPC475294
0.55	Remote Similarity	NPC257457
0.55	Remote Similarity	NPC311554
0.5488	Remote Similarity	NPC486347
0.5362	Remote Similarity	NPC479417
0.5309	Remote Similarity	NPC148458
0.5263	Remote Similarity	NPC87351
0.5195	Remote Similarity	NPC474720
0.5128	Remote Similarity	NPC488646
0.5122	Remote Similarity	NPC482855

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC196528 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	7161
0.1-0.2	1957
0.2-0.3	32
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