NPASS Compound

Natural Product: NPC54225

Natural Product ID	NPC54225
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	GZMNAJUVLAIUAJ-ROZLUKNESA-N
IUPAC Name	n.a.
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	n.a.
PubChem CID	n.a.
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000012] Lipids and lipid-like molecules [CHEMONTID:0000258] Steroids and steroid derivatives [CHEMONTID:0001013] Steroidal glycosides [CHEMONTID:0002364] Steroidal saponins

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 93 99 0 0 0 0 0 0 0 0999 V2000 9.2124 0.4958 1.3004 C 0 0 0 0 0 0 0 0 0 0 0 0 7.9932 0.4164 0.4177 C 0 0 1 0 0 0 0 0 0 0 0 0 7.4952 -0.9815 0.2544 C 0 0 0 0 0 0 0 0 0 0 0 0 6.1131 -1.0116 -0.3143 C 0 0 0 0 0 0 0 0 0 0 0 0 5.1729 -0.0511 0.3645 C 0 0 2 0 0 0 0 0 0 0 0 0 3.9860 -0.7811 0.9579 C 0 0 1 0 0 0 0 0 0 0 0 0 4.0454 -0.7439 2.4787 C 0 0 0 0 0 0 0 0 0 0 0 0 2.8101 0.0258 0.5277 C 0 0 1 0 0 0 0 0 0 0 0 0 3.4076 1.2452 -0.0913 C 0 0 2 0 0 0 0 0 0 0 0 0 2.4942 1.6389 -1.2236 C 0 0 0 0 0 0 0 0 0 0 0 0 1.4336 0.5727 -1.3347 C 0 0 2 0 0 0 0 0 0 0 0 0 0.1210 1.0469 -0.7868 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.4420 1.9874 -1.8477 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.7040 2.5672 -1.2642 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.7081 1.4527 -1.2217 C 0 0 2 0 0 0 0 0 0 0 0 0 -3.9567 2.0501 -0.5538 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.7888 2.2011 0.9222 C 0 0 1 0 0 0 0 0 0 0 0 0 -3.0148 1.0885 1.5468 C 0 0 2 0 0 0 0 0 0 0 0 0 -3.1112 -0.1118 0.6035 C 0 0 2 0 0 0 0 0 0 0 0 0 -2.2725 0.1756 -0.6264 C 0 0 1 0 0 0 0 0 0 0 0 0 -2.6526 -0.9411 -1.6130 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.8147 0.0029 -0.3464 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.2723 -1.3503 -0.8234 C 0 0 0 0 0 0 0 0 0 0 0 0 1.0428 -1.5471 -0.0551 C 0 0 0 0 0 0 0 0 0 0 0 0 2.0318 -0.5881 -0.6108 C 0 0 2 0 0 0 0 0 0 0 0 0 2.9173 -1.3376 -1.5852 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.4300 -0.3815 0.3602 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.8473 -1.6144 0.8529 C 0 0 1 0 0 0 0 0 0 0 0 0 -5.9925 -1.5172 1.8349 C 0 0 1 0 0 0 0 0 0 0 0 0 -7.1519 -0.8566 1.1762 C 0 0 2 0 0 0 0 0 0 0 0 0 -7.5687 -1.7169 -0.0088 C 0 0 2 0 0 0 0 0 0 0 0 0 -6.3379 -1.9184 -0.8991 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.2787 -2.4252 -0.1887 O 0 0 0 0 0 0 0 0 0 0 0 0 -8.5736 -1.1554 -0.7543 O 0 0 0 0 0 0 0 0 0 0 0 0 -6.7655 0.3818 0.6809 O 0 0 0 0 0 0 0 0 0 0 0 0 -6.3714 -2.8482 2.1123 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.5438 0.7788 2.7748 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.2686 3.4593 1.2249 O 0 0 0 0 0 0 0 0 0 0 0 0 4.6800 0.9138 -0.4881 O 0 0 0 0 0 0 0 0 0 0 0 0 5.8656 0.5661 1.4044 O 0 0 0 0 0 0 0 0 0 0 0 0 6.9189 1.3315 0.9667 C 0 0 0 0 0 0 0 0 0 0 0 0 8.8862 0.6858 2.3462 H 0 0 0 0 0 0 0 0 0 0 0 0 9.8316 1.3542 0.9894 H 0 0 0 0 0 0 0 0 0 0 0 0 9.7891 -0.4492 1.3180 H 0 0 0 0 0 0 0 0 0 0 0 0 8.2654 0.8122 -0.5887 H 0 0 0 0 0 0 0 0 0 0 0 0 8.1653 -1.4886 -0.4991 H 0 0 0 0 0 0 0 0 0 0 0 0 7.5992 -1.5942 1.1918 H 0 0 0 0 0 0 0 0 0 0 0 0 6.1689 -0.7373 -1.3859 H 0 0 0 0 0 0 0 0 0 0 0 0 5.7495 -2.0618 -0.2792 H 0 0 0 0 0 0 0 0 0 0 0 0 3.9525 -1.8378 0.6709 H 0 0 0 0 0 0 0 0 0 0 0 0 4.8411 -1.4547 2.7878 H 0 0 0 0 0 0 0 0 0 0 0 0 4.2392 0.2949 2.7754 H 0 0 0 0 0 0 0 0 0 0 0 0 3.0551 -1.0622 2.8634 H 0 0 0 0 0 0 0 0 0 0 0 0 2.0952 0.2557 1.3334 H 0 0 0 0 0 0 0 0 0 0 0 0 3.5103 2.0736 0.6641 H 0 0 0 0 0 0 0 0 0 0 0 0 2.0508 2.6199 -0.9632 H 0 0 0 0 0 0 0 0 0 0 0 0 3.0436 1.7896 -2.1747 H 0 0 0 0 0 0 0 0 0 0 0 0 1.3354 0.3343 -2.4281 H 0 0 0 0 0 0 0 0 0 0 0 0 0.3811 1.7377 0.0717 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.6999 1.4838 -2.7758 H 0 0 0 0 0 0 0 0 0 0 0 0 0.2820 2.8208 -1.9495 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.0711 3.3243 -1.9893 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.5500 3.0821 -0.3136 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.0386 1.3176 -2.2967 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.0281 3.0918 -0.9870 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.8659 1.5484 -0.8893 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.8208 2.1931 1.3776 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.9394 1.3156 1.6871 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.6253 -0.9546 1.1594 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.6691 -0.6502 -2.0089 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.9799 -0.9324 -2.4877 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.7777 -1.9106 -1.1393 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.7218 -0.0807 0.7810 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.8972 -2.1982 -0.4804 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.0672 -1.3292 -1.8936 H 0 0 0 0 0 0 0 0 0 0 0 0 0.8530 -1.3810 1.0140 H 0 0 0 0 0 0 0 0 0 0 0 0 1.3261 -2.6131 -0.2153 H 0 0 0 0 0 0 0 0 0 0 0 0 2.2717 -1.5715 -2.4681 H 0 0 0 0 0 0 0 0 0 0 0 0 3.2711 -2.3036 -1.1982 H 0 0 0 0 0 0 0 0 0 0 0 0 3.7374 -0.7022 -1.9835 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.9950 -2.1580 1.3432 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.6919 -1.0529 2.7918 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.0228 -0.7689 1.8672 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.8106 -2.7188 0.4037 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.1009 -0.9947 -1.4682 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.6379 -2.6862 -1.6420 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.3030 -0.9246 -1.6887 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.9664 0.4875 -0.2958 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.5914 -3.2644 2.5856 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.8419 0.6609 3.4628 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.7410 4.0949 0.6031 H 0 0 0 0 0 0 0 0 0 0 0 0 7.3024 1.8988 1.8510 H 0 0 0 0 0 0 0 0 0 0 0 0 6.5781 2.0849 0.2402 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 1 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 15 16 1 0 16 17 1 0 17 18 1 0 18 19 1 0 19 20 1 0 20 21 1 6 20 22 1 0 22 23 1 0 23 24 1 0 24 25 1 0 25 26 1 6 19 27 1 0 27 28 1 0 28 29 1 0 29 30 1 0 30 31 1 0 31 32 1 0 32 33 1 0 31 34 1 0 30 35 1 0 29 36 1 0 18 37 1 0 17 38 1 0 9 39 1 0 5 40 1 1 40 41 1 0 41 2 1 0 39 5 1 0 25 8 1 0 33 28 1 0 25 11 1 0 22 12 1 0 20 15 1 0 1 42 1 0 1 43 1 0 1 44 1 0 2 45 1 6 3 46 1 0 3 47 1 0 4 48 1 0 4 49 1 0 6 50 1 1 7 51 1 0 7 52 1 0 7 53 1 0 8 54 1 1 9 55 1 1 10 56 1 0 10 57 1 0 11 58 1 6 12 59 1 1 13 60 1 0 13 61 1 0 14 62 1 0 14 63 1 0 15 64 1 6 16 65 1 0 16 66 1 0 17 67 1 1 18 68 1 1 19 69 1 1 21 70 1 0 21 71 1 0 21 72 1 0 22 73 1 1 23 74 1 0 23 75 1 0 24 76 1 0 24 77 1 0 26 78 1 0 26 79 1 0 26 80 1 0 28 81 1 1 29 82 1 1 30 83 1 1 31 84 1 1 32 85 1 0 32 86 1 0 34 87 1 0 35 88 1 0 36 89 1 0 37 90 1 0 38 91 1 0 41 92 1 0 41 93 1 0 M END

Standard InCHIKey	GZMNAJUVLAIUAJ-ROZLUKNESA-N
Standard InCHI	InChI=1S/C32H52O9/c1-15-7-10-32(39-13-15)16(2)24-23(41-32)12-20-18-6-5-17-11-21(33)26(36)28(31(17,4)19(18)8-9-30(20,24)3)40-29-27(37)25(35)22(34)14-38-29/h15-29,33-37H,5-14H2,1-4H3/t15-,16-,17+,18-,19-,20+,21-,22-,23-,24-,25-,26+,27+,28+,29-,30-,31-,32+/m0/s1
SMILES	C[C@H]1CC[C@@]2([C@@H](C)[C@H]3[C@H](C[C@@H]4[C@H]5CC[C@@H]6C[C@@H]([C@H]([C@H]([C@]6(C)[C@H]5CC[C@]34C)O[C@H]3[C@@H]([C@H]([C@H](CO3)O)O)O)O)O)O2)OC1

Calculated Properties

Physi-Chem Properties

Molecular Weight:	580.36	Volume:	581.245 ? Van der Waals volume.
Dense:	0.998	LogP:	3.889 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	4.174 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-5.533 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	2.0	Rigid Bonds:	36.0
TPSA:	138.07 ? Topological Polar Surface Area.	H-Bond Acceptor:	9.0
H-Bond Donor:	5.0	Rings:	7.0
Heavy Atoms:	9.0

MedChem Properties

QED Drug-Likeness Score:	0.333	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	6.007	Fsp³:	1.0
MCE-18:	174.375 ? 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:	0.715	Fluc inhibitor:	0.0 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.076 ? 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:	0.174	Promiscuous compounds:	0.032

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.869	MDCK Permeability:	-5.037
Pgp-inhibitor:	0.02	Pgp-substrate:	0.408
PAMPA:	0.971 ? 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%):	0.232	30% Bioavailability (F30%):	0.525
50% Bioavailability (F50%):	0.982

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.011	MRP1:	0.331
Plasma Protein Binding (PPB):	66.455%	Volume Distribution (VD):	-0.332
Fu:	30.847% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	1.0
OATP1B3 inhibitor:	1.0	BCRP inhibitor:	0.423
BSEP inhibitor:	0.474

ADMET: Metabolism

CYP1A2-inhibitor:	0.0	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	0.001	CYP2C19-substrate:	0.0
CYP2C9-inhibitor:	0.0	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.001
CYP3A4-inhibitor:	0.057	CYP3A4-substrate:	0.999
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.997
HLM stability:	0.121 ? 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):

2.777

Half-life (T1/2):

2.242

ADMET: Toxicity

hERG Blockers:	0.081	hERG Blockers (10um):	0.358
Human Hepatotoxicity (H-HT):	0.542	Drug-induced Liver Injury (DILI):	0.693
AMES Toxicity:	0.58	Rat Oral Acute Toxicity:	0.126
Maximum Recommended Daily Dose:	0.333	Skin Sensitization:	0.999
Carcinogencity:	0.449	Eye Corrosion:	0.0
Eye Irritation:	0.168	Respiratory Toxicity:	0.143
Drug-induced Neurotoxicity:	0.012	Ototoxicity:	0.896
Hematotoxicity:	0.204	Drug-induced Nephrotoxicity:	0.715
Genotoxicity:	0.009	RPMI-8226 Immunitoxicity:	0.217
A549 Cytotoxicity:	0.718	Hek293 Cytotoxicity:	0.791
BCF:	2.252 ? 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:	3.813 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.796 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.418 ? 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
NPO22018	Hydrangea chinensis	Species	Hydrangeaceae	Eukaryota	Roots	n.a.	n.a.	PMID[11473431]
NPO20244	Melicope semecarpifolia	Species	Rutaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[11575945]
NPO20244	Melicope semecarpifolia	Species	Rutaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[18163582]
NPO26918	Taricha granulosa	Species	Salamandridae	Eukaryota	n.a.	n.a.	n.a.	PMID[32896120]
NPO17338	Solanum asperum	Species	Solanaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO14627	Caloscypha fulgens	Species	Caloscyphaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO22836	Alpinia mutica	Species	Zingiberaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO20244	Melicope semecarpifolia	Species	Rutaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO22018	Hydrangea chinensis	Species	Hydrangeaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO22402	Lupinus mutabilis	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO16398	Nicotiana alata	Species	Solanaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO12967	Reseda suffruticosa	Species	Resedaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO20565	Aplysina fulva	Species	Aplysinidae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO23001	Halimium umbellatum	Species	Cistaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO20244	Melicope semecarpifolia	Species	Rutaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO22018	Hydrangea chinensis	Species	Hydrangeaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO20244	Melicope semecarpifolia	Species	Rutaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO22018	Hydrangea chinensis	Species	Hydrangeaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO17338	Solanum asperum	Species	Solanaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO16398	Nicotiana alata	Species	Solanaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO1463	Corethrodendron scoparium	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO22402	Lupinus mutabilis	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO20244	Melicope semecarpifolia	Species	Rutaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO22836	Alpinia mutica	Species	Zingiberaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO23001	Halimium umbellatum	Species	Cistaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO18364	Genista lusitanica	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO12967	Reseda suffruticosa	Species	Resedaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO14902	Pteris marginata	Species	Pteridaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO19482	Tapinoma nigerrimum	Species	Formicidae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO20402	Ageratina gilbertii	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO14627	Caloscypha fulgens	Species	Caloscyphaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO26918	Taricha granulosa	Species	Salamandridae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO23067	Shorea maranti	Species	Dipterocarpaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO22018	Hydrangea chinensis	Species	Hydrangeaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO20565	Aplysina fulva	Species	Aplysinidae	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

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

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 NPC54225 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	25781
0.1-0.2	21883
0.2-0.3	1894
0.3-0.4	138
0.4-0.5	87
0.5-0.6	58
0.6-0.7	11
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
0.7692	Intermediate Similarity	NPC481418
0.6667	Remote Similarity	NPC88962
0.6628	Remote Similarity	NPC177834
0.6591	Remote Similarity	NPC250393
0.6512	Remote Similarity	NPC481423
0.6429	Remote Similarity	NPC473774
0.6429	Remote Similarity	NPC481419
0.6429	Remote Similarity	NPC481417
0.6353	Remote Similarity	NPC24960
0.6133	Remote Similarity	NPC227260
0.6022	Remote Similarity	NPC264101
0.6	Remote Similarity	NPC485591
0.5921	Remote Similarity	NPC248944
0.5921	Remote Similarity	NPC7479
0.5921	Remote Similarity	NPC257296
0.5876	Remote Similarity	NPC475351
0.587	Remote Similarity	NPC312678
0.587	Remote Similarity	NPC253268
0.5862	Remote Similarity	NPC481420
0.5862	Remote Similarity	NPC481421
0.5816	Remote Similarity	NPC473601
0.58	Remote Similarity	NPC471464
0.5686	Remote Similarity	NPC97700
0.5686	Remote Similarity	NPC30856
0.5631	Remote Similarity	NPC115165
0.5588	Remote Similarity	NPC128572
0.5579	Remote Similarity	NPC211354
0.5579	Remote Similarity	NPC107188
0.5543	Remote Similarity	NPC325828
0.5532	Remote Similarity	NPC473616
0.5524	Remote Similarity	NPC475625
0.5521	Remote Similarity	NPC485590
0.5517	Remote Similarity	NPC144790
0.5517	Remote Similarity	NPC149400
0.5472	Remote Similarity	NPC232037
0.5464	Remote Similarity	NPC215408
0.5455	Remote Similarity	NPC277715
0.5443	Remote Similarity	NPC296734
0.5435	Remote Similarity	NPC481424
0.5435	Remote Similarity	NPC481422
0.5377	Remote Similarity	NPC473518
0.5376	Remote Similarity	NPC297348
0.5376	Remote Similarity	NPC249204
0.5376	Remote Similarity	NPC48339
0.5376	Remote Similarity	NPC141769
0.5376	Remote Similarity	NPC477547
0.537	Remote Similarity	NPC476112
0.537	Remote Similarity	NPC307534
0.5347	Remote Similarity	NPC202898
0.5321	Remote Similarity	NPC132080
0.5319	Remote Similarity	NPC294686
0.5319	Remote Similarity	NPC234352
0.5263	Remote Similarity	NPC477451
0.525	Remote Similarity	NPC273290
0.525	Remote Similarity	NPC232044
0.5238	Remote Similarity	NPC294129
0.5213	Remote Similarity	NPC13190
0.5208	Remote Similarity	NPC222731
0.5155	Remote Similarity	NPC206003
0.5155	Remote Similarity	NPC473610
0.5152	Remote Similarity	NPC107962
0.5149	Remote Similarity	NPC160426
0.5102	Remote Similarity	NPC19400
0.5098	Remote Similarity	NPC485605
0.5093	Remote Similarity	NPC116756
0.506	Remote Similarity	NPC305808
0.505	Remote Similarity	NPC70204
0.5048	Remote Similarity	NPC51172
0.5048	Remote Similarity	NPC49032
0.5046	Remote Similarity	NPC232611

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC54225 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	7599
0.1-0.2	1485
0.2-0.3	62
0.3-0.4	0
0.4-0.5	2
0.5-0.6	2
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
0.5921	Remote Similarity	NPD6928	Phase 2
0.5543	Remote Similarity	NPD8171	Phase 2

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